chr12-20862972-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.727+118C>G		intron_variant	Intron 8 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.727+118C>G		intron_variant	Intron 6 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2	c.643+118C>G		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>G		intron_variant	Intron 8 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.727+118C>G		intron_variant	Intron 6 of 15	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15917 AN: 152012 Hom.: 1128 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0282 AC: 284 AN: 10080

Gnomad4 AMR exome AF: 0.0829 AC: 1034 AN: 12476

Gnomad4 ASJ exome AF: 0.195 AC: 2096 AN: 10752

Gnomad4 EAS exome AF: 0.000230 AC: 6 AN: 26118

Gnomad4 SAS exome AF: 0.0653 AC: 1184 AN: 18132

Gnomad4 FIN exome AF: 0.101 AC: 3528 AN: 34816

Gnomad4 NFE exome AF: 0.152 AC: 34606 AN: 227650

Gnomad4 Remaining exome AF: 0.133 AC: 2789 AN: 20984

GnomAD4 genome AF: 0.105 AC: 15912 AN: 152128 Hom.: 1126 Cov.: 32 AF XY: 0.100 AC XY: 7448 AN XY: 74382

Gnomad4 AFR AF: 0.0291 AC: 0.0291014 AN: 0.0291014

Gnomad4 AMR AF: 0.109 AC: 0.108986 AN: 0.108986

Gnomad4 ASJ AF: 0.193 AC: 0.192795 AN: 0.192795

Gnomad4 EAS AF: 0.00174 AC: 0.00173678 AN: 0.00173678

Gnomad4 SAS AF: 0.0682 AC: 0.0681724 AN: 0.0681724

Gnomad4 FIN AF: 0.102 AC: 0.102135 AN: 0.102135

Gnomad4 NFE AF: 0.153 AC: 0.15344 AN: 0.15344

Gnomad4 OTH AF: 0.136 AC: 0.135633 AN: 0.135633

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
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV53945888; COSMIC: COSV53945888;