Variant 12-20862972-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019844.4(SLCO1B3):c.727+118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 515,374 control chromosomes in the GnomAD database, including 4,654 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1126 hom., cov: 32)

Exomes 𝑓: 0.13 ( 3528 hom. )

Consequence

SLCO1B3
NM_019844.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.10

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SLCO1B3	NM_019844.4 linkuse as main transcript	c.727+118C>G	intron_variant	ENST00000381545.8	NP_062818.1	Q9NPD5-1B3KP78
SLCO1B3-SLCO1B7	NM_001371097.1 linkuse as main transcript	c.727+118C>G	intron_variant		NP_001358026.1
SLCO1B3	NM_001349920.2 linkuse as main transcript	c.643+118C>G	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.727+118C>G		intron_variant		2	NM_019844.4	ENSP00000370956.4		Q9NPD5-1
SLCO1B3-SLCO1B7	ENST00000540229.1 linkuse as main transcript	c.727+118C>G		intron_variant		2		ENSP00000441269.1		A0A0A6YYJ9

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15917

AN:

152012

Hom.:

1128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0679

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.127

AC:

46083

AN:

363246

Hom.:

3528

AF XY:

0.128

AC XY:

24214

AN XY:

189904

show subpopulations

Gnomad4 AFR exome

AF:

0.0282

Gnomad4 AMR exome

AF:

0.0829

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.000230

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.105

AC:

15912

AN:

152128

Hom.:

1126

Cov.:

AF XY:

0.100

AC XY:

7448

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0291

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0682

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.153

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.120

Hom.:

158

Bravo

AF:

0.104

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.28

DANN

Benign

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over