rs4149118

Positions:

• chr12-20858647-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.193

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: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 (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.359+76G>A		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.359+76G>A		intron_variant			NP_001358026.1
SLCO1B3	NM_001349920.2	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	c.359+76G>A		intron_variant		2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.359+76G>A		intron_variant		2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81425 AN: 151444 Hom.: 24387 Cov.: 31

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

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.: 31 AF XY: 0.538 AC XY: 39838 AN XY: 74072

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

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

Other links and lift over

dbSNP: rs4149118; hg19: chr12-21011581; COSMIC: COSV53936619; COSMIC: COSV53936619;