Variant 12-20858647-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019844.4(SLCO1B3):c.359+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,384,570 control chromosomes in the GnomAD database, including 296,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 24387 hom., cov: 31)

Exomes 𝑓: 0.66 ( 271907 hom. )

Consequence

SLCO1B3
NM_019844.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.193

Variant links:

Genes affected

SLCO1B3 (HGNC:10961): (solute carrier organic anion transporter family member 1B3) This gene encodes a liver-specific member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of endogenous and xenobiotic compounds and plays a critical role in bile acid and bilirubin transport. Mutations in this gene are a cause of Rotor type hyperbilirubinemia. Alternative splicing of this gene and the use of alternative promoters results in transcript variants encoding different isoforms that differ in their tissue specificity. [provided by RefSeq, Mar 2017]

SLCO1B3 links:

SLCO1B3-SLCO1B7 (HGNC:54403): (SLCO1B3-SLCO1B7 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring SLCO1B3 (solute carrier organic anion transporter family member 1B3) and SLCO1B7 (solute carrier organic anion transporter family member 1B7 (putative)) genes on chromosome 12. The readthrough transcript encodes a protein that shares sequence identity with both the upstream and downstream genes. [provided by RefSeq, Jun 2019]

SLCO1B3-SLCO1B7 links:

SLCO1B3 (HGNC:):

SLCO1B3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-20858647-G-A is Benign according to our data. Variant chr12-20858647-G-A is described in ClinVar as [Benign]. Clinvar id is 1286427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLCO1B3	NM_019844.4 linkuse as main transcript	c.359+76G>A	intron_variant	ENST00000381545.8	NP_062818.1	Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.359+76G>A	intron_variant		NP_001358026.1
SLCO1B3	NM_001349920.2 linkuse as main transcript	c.275+76G>A	intron_variant		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.359+76G>A		intron_variant		2	NM_019844.4	ENSP00000370956.4		Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1 linkuse as main transcript	c.359+76G>A		intron_variant		2		ENSP00000441269.1		A0A0A6YYJ9

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81425

AN:

151444

Hom.:

24387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.617

Gnomad AMR

AF:

0.607

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.561

GnomAD4 exome

AF:

0.659

AC:

812740

AN:

1233006

Hom.:

271907

AF XY:

0.663

AC XY:

409835

AN XY:

617812

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.635

Gnomad4 ASJ exome

AF:

0.669

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.776

Gnomad4 FIN exome

AF:

0.569

Gnomad4 NFE exome

AF:

0.675

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.537

AC:

81431

AN:

151564

Hom.:

24387

Cov.:

AF XY:

0.538

AC XY:

39838

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.673

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.767

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.667

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.651

Hom.:

64429

Bravo

AF:

0.527

Asia WGS

AF:

0.611

AC:

2117

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.0

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over