rs17680137

Variant names:

• chr12-20862972-C-A
• rs17680137
• NM_019844.4:c.727+118C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-20862972-C-A
• chr12-20862972-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019844.4(SLCO1B3):​c.727+118C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 363,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.727+118C>A		intron_variant	Intron 8 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.727+118C>A		intron_variant	Intron 6 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2	c.643+118C>A		intron_variant	Intron 6 of 13		NP_001336849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.727+118C>A		intron_variant	Intron 8 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.727+118C>A		intron_variant	Intron 6 of 15	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000440 AC: 16 AN: 363832 Hom.: 0 AF XY: 0.0000421 AC XY: 8 AN XY: 190180

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000613

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.54

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: rs17680137; hg19: chr12-21015906;