chr12-20862930-C-G

Variant names:

• chr12-20862930-C-G
• rs71583718
• NM_019844.4:c.727+76C>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+76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 750,380 control chromosomes in the GnomAD database, including 1,181 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 0.043 (227 hom., cov: 32)
  • Exomes 𝑓: 0.043 (954 hom.)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• Publications: 1 publications found

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.727+76C>G		intron_variant	Intron 8 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.727+76C>G		intron_variant	Intron 6 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2	c.643+76C>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+76C>G		intron_variant	Intron 8 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.727+76C>G		intron_variant	Intron 6 of 15	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6607 AN: 152076 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.0194

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0432 AC: 25831 AN: 598186 Hom.: 954 AF XY: 0.0423 AC XY: 13361 AN XY: 316016

African (AFR) AF: 0.0174 AC: 289 AN: 16648

American (AMR) AF: 0.0736 AC: 2041 AN: 27714

Ashkenazi Jewish (ASJ) AF: 0.0224 AC: 357 AN: 15958

East Asian (EAS) AF: 0.137 AC: 4449 AN: 32564

South Asian (SAS) AF: 0.0359 AC: 1570 AN: 43696

European-Finnish (FIN) AF: 0.0893 AC: 4205 AN: 47108

Middle Eastern (MID) AF: 0.0613 AC: 230 AN: 3750

European-Non Finnish (NFE) AF: 0.0294 AC: 11184 AN: 380136

Other (OTH) AF: 0.0492 AC: 1506 AN: 30612

GnomAD4 genome AF: 0.0434 AC: 6609 AN: 152194 Hom.: 227 Cov.: 32 AF XY: 0.0475 AC XY: 3537 AN XY: 74410

African (AFR) AF: 0.0194 AC: 806 AN: 41544

American (AMR) AF: 0.0817 AC: 1248 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3468

East Asian (EAS) AF: 0.178 AC: 919 AN: 5168

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4822

European-Finnish (FIN) AF: 0.0976 AC: 1033 AN: 10586

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0316 AC: 2152 AN: 68002

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0357 Hom.: 12

Bravo AF: 0.0412

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.024
DANN	Benign	0.37
PhyloP100		-2.7
PromoterAI		0.0010	Neutral
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

Other links and lift over

dbSNP: rs71583718; hg19: chr12-21015864; COSMIC: COSV53940318; COSMIC: COSV53940318;