dbSNP rs3764007: SLCO1B3:c.481+91T>A (chr12-20861229-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_019844.4(SLCO1B3):c.481+91T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,166,428 control chromosomes in the GnomAD database, including 399,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 42510 hom., cov: 33)

Exomes 𝑓: 0.84 ( 356993 hom. )

Consequence

SLCO1B3
NM_019844.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.510

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-20861229-T-A is Benign according to our data. Variant chr12-20861229-T-A is described in ClinVar as [Benign]. Clinvar id is 1247275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4 link	c.481+91T>A	intron_variant	Intron 6 of 15	ENST00000381545.8	NP_062818.1	Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7	NM_001371097.1 link	c.481+91T>A	intron_variant	Intron 4 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2 link	c.397+91T>A	intron_variant	Intron 4 of 13		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8 link	c.481+91T>A		intron_variant	Intron 6 of 15	2	NM_019844.4	ENSP00000370956.4		Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1 link	c.481+91T>A		intron_variant	Intron 4 of 15	2		ENSP00000441269.1		A0A0A6YYJ9

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110166

AN:

151968

Hom.:

42513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.855

Gnomad AMR

AF:

0.812

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.898

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.853

Gnomad OTH

AF:

0.781

GnomAD4 exome

AF:

0.835

AC:

847044

AN:

1014342

Hom.:

356993

AF XY:

0.840

AC XY:

427738

AN XY:

509420

show subpopulations

Gnomad4 AFR exome

AF:

0.403

Gnomad4 AMR exome

AF:

0.804

Gnomad4 ASJ exome

AF:

0.893

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.907

Gnomad4 FIN exome

AF:

0.764

Gnomad4 NFE exome

AF:

0.851

Gnomad4 OTH exome

AF:

0.821

GnomAD4 genome

AF:

0.725

AC:

110190

AN:

152086

Hom.:

42510

Cov.:

AF XY:

0.724

AC XY:

53803

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.435

Gnomad4 AMR

AF:

0.812

Gnomad4 ASJ

AF:

0.890

Gnomad4 EAS

AF:

0.719

Gnomad4 SAS

AF:

0.900

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.853

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.684

Hom.:

2233

Bravo

AF:

0.717

Asia WGS

AF:

0.764

AC:

2655

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.1

DANN

Benign

0.86

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