NC_000012.11:g.21014093_21014094insLINE1 AND constitutional indocyanine green excretory defect

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 20, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003334396.1

Allele description [Variation Report for NC_000012.11:g.21014093_21014094insLINE1]

NC_000012.11:g.21014093_21014094insLINE1

Gene:

SLCO1B3:solute carrier organic anion transporter family member 1B3 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

12p12.2

Genomic location:

Chr12: 21014093 - 21014094 (on Assembly GRCh37)

Preferred name:

NC_000012.11:g.21014093_21014094insLINE1

HGVS:

NC_000012.11:g.21014093_21014094insLINE1
NC_000012.11:g.21014093_21014094insLINE1

Note:

The variant length was curated by NCBI. LINE elements are 4000-7000 bp; a typical LINE is 6000 bp.

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Observations:

Condition(s)

Name:: constitutional indocyanine green excretory defect
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001426413	Liver Center, Tokai University School of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 20, 2016)	inherited	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 27863442

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001426413

Liver Center, Tokai University School of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 20, 2016)

inherited

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Japanese	inherited	yes	4	4	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Loss of organic anion transporting polypeptide 1B3 function causes marked delay in indocyanine green clearance without any clinical symptoms.

Kagawa T, Adachi Y, Hashimoto N, Mitsui H, Ohashi T, Yoneda M, Hasegawa I, Hirose S, Tsuruya K, Anzai K, Mine T.

Hepatology. 2017 Mar;65(3):1065-1068. doi: 10.1002/hep.28950. Epub 2017 Jan 6. No abstract available.

PubMed [citation]

PMID:: 27863442
PMCID:: PMC5324621

Details of each submission

From Liver Center, Tokai University School of Medicine, SCV001426413.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Japanese	4	not provided	not provided	clinical testing	PubMed (2)

Description

Hepatic OATP1B3 expression was absent.

Description

All of four Japanese patients with constitutional indocyanine green (ICG) excretory defect, manifesting markedly impaired ICG clearance, had a homozygous insertion of ~6.1-kbp LINE-1 retrotranspozon (L1) in intron 5 of SLCO1B3 gene without any pathological variants in SLCO1B1 and SLC10A1 genes. Immunohistochemistry confirmed the absence of hepatic OATP1B3 expression. The allele frequency of this variant was 0.054 in a Japanese population. In summary, the L1 insertion in intron 5 of SLCO1B3 gene meets our criteria to be classified as pathogenic based upon segregation studies and functional analysis.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		4	not provided	4	not provided

Last Updated: Oct 21, 2023

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