rs60571683

chr12-20916115-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019844.4(SLCO1B3):c.1977G>A(p.Ser659=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 1,612,444 control chromosomes in the GnomAD database, including 2,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (177 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2106 hom.)
• Consequence: SLCO1B3 NM_019844.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.782

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-SLCO1B7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-20916115-G-A is Benign according to our data. Variant chr12-20916115-G-A is described in ClinVar as [Benign]. Clinvar id is 307914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.782 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.1977G>A	p.Ser659=	synonymous_variant	16/16	ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1	c.1865+14648G>A		intron_variant
LOC124902894	XM_047429949.1	c.-58+14648G>A		intron_variant
SLCO1B3	NM_001349920.2	c.1893G>A	p.Ser631=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.1977G>A	p.Ser659=	synonymous_variant	16/16	2	NM_019844.4	P1
SLCO1B3	ENST00000261196.6	c.1977G>A	p.Ser659=	synonymous_variant	14/14	1		P1

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5836 AN: 151990 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0436

GnomAD3 exomes AF: 0.0379 AC: 9487 AN: 250602 Hom.: 277 AF XY: 0.0380 AC XY: 5147 AN XY: 135452

Gnomad AFR exome AF: 0.00875

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.000328

Gnomad SAS exome AF: 0.00817

Gnomad FIN exome AF: 0.0123

Gnomad NFE exome AF: 0.0555

Gnomad OTH exome AF: 0.0520

GnomAD4 exome AF: 0.0486 AC: 70986 AN: 1460338 Hom.: 2106 Cov.: 30 AF XY: 0.0477 AC XY: 34644 AN XY: 726514

Gnomad4 AFR exome AF: 0.00804

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0897

Gnomad4 EAS exome AF: 0.000278

Gnomad4 SAS exome AF: 0.00885

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.0504

GnomAD4 genome AF: 0.0383 AC: 5830 AN: 152106 Hom.: 177 Cov.: 32 AF XY: 0.0361 AC XY: 2683 AN XY: 74352

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0607

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00954

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0513 Hom.: 250

Bravo AF: 0.0415

Asia WGS AF: 0.00405 AC: 14 AN: 3474

EpiCase AF: 0.0595

EpiControl AF: 0.0643

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Rotor syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 27, 2023	- -

SLCO1B3-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.5
Dann	Benign	0.41

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

Other links and lift over

dbSNP: rs60571683; hg19: chr12-21069049; COSMIC: COSV53933479;