12-20815894-C-T

Position:

• chr12-20815894-C-T

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.84+72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 844,514 control chromosomes in the GnomAD database, including 385,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (63027 hom., cov: 32)
  • Exomes 𝑓: 0.96 (322416 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.447

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-20815894-C-T is Benign according to our data. Variant chr12-20815894-C-T is described in ClinVar as [Benign]. Clinvar id is 1274436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.84+72C>T		intron_variant		ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.84+72C>T		intron_variant			NP_001358026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.84+72C>T		intron_variant		2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.84+72C>T		intron_variant		2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137499 AN: 152122 Hom.: 62982 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.917

GnomAD4 exome AF: 0.964 AC: 667434 AN: 692274 Hom.: 322416 AF XY: 0.964 AC XY: 349219 AN XY: 362188

Gnomad4 AFR exome AF: 0.715

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.970

Gnomad4 EAS exome AF: 0.993

Gnomad4 SAS exome AF: 0.954

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.972

Gnomad4 OTH exome AF: 0.953

GnomAD4 genome AF: 0.904 AC: 137598 AN: 152240 Hom.: 63027 Cov.: 32 AF XY: 0.907 AC XY: 67479 AN XY: 74430

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.954

Gnomad4 ASJ AF: 0.972

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.918

Alfa AF: 0.931 Hom.: 19257

Bravo AF: 0.895

Asia WGS AF: 0.956 AC: 3303 AN: 3458

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	-0.83
CADD	Benign	5.1
DANN	Benign	0.50

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: rs10734710; hg19: chr12-20968828;