Variant chr12-20815946-A-T 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.84+124A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 491,284 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 127 hom., cov: 33)

Exomes 𝑓: 0.034 ( 304 hom. )

Consequence

SLCO1B3
NM_019844.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.219

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:):

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=-0.82).

BP6

Variant 12-20815946-A-T is Benign according to our data. Variant chr12-20815946-A-T is described in ClinVar as [Benign]. Clinvar id is 1287212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4 linkuse as main transcript	c.84+124A>T		intron_variant		ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.84+124A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8 linkuse as main transcript	c.84+124A>T	intron_variant	2	NM_019844.4	P1	Q9NPD5-1
SLCO1B3	ENST00000261196.6 linkuse as main transcript	c.84+124A>T	intron_variant	1		P1	Q9NPD5-1
SLCO1B3	ENST00000540853.5 linkuse as main transcript	c.84+124A>T	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5459

AN:

152244

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0186

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.0991

Gnomad SAS

AF:

0.0312

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.0339

AC:

11476

AN:

338922

Hom.:

304

AF XY:

0.0327

AC XY:

5830

AN XY:

178188

show subpopulations

Gnomad4 AFR exome

AF:

0.0350

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0583

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.0139

Gnomad4 FIN exome

AF:

0.0571

Gnomad4 NFE exome

AF:

0.0246

Gnomad4 OTH exome

AF:

0.0299

GnomAD4 genome

AF:

0.0358

AC:

5458

AN:

152362

Hom.:

127

Cov.:

AF XY:

0.0374

AC XY:

2786

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0374

Gnomad4 AMR

AF:

0.0186

Gnomad4 ASJ

AF:

0.0712

Gnomad4 EAS

AF:

0.0988

Gnomad4 SAS

AF:

0.0304

Gnomad4 FIN

AF:

0.0644

Gnomad4 NFE

AF:

0.0286

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0196

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.0590

AC:

205

AN:

3474

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

-0.82

CADD

Benign

1.9

DANN

Benign

0.64

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