12-20869264-A-C

Variant names:

• chr12-20869264-A-C
• rs7953425
• NM_019844.4:c.728-5971A>C

Variant summary

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

The NM_019844.4(SLCO1B3):​c.728-5971A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,100 control chromosomes in the GnomAD database, including 42,506 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 0.72 (42506 hom., cov: 32)
• Consequence: SLCO1B3 NM_019844.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 3 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=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B3	NM_019844.4	c.728-5971A>C		intron_variant	Intron 8 of 15	ENST00000381545.8	NP_062818.1
SLCO1B3-SLCO1B7	NM_001371097.1	c.728-5971A>C		intron_variant	Intron 6 of 15		NP_001358026.1
SLCO1B3	NM_001349920.2	c.644-5971A>C		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.728-5971A>C		intron_variant	Intron 8 of 15	2	NM_019844.4	ENSP00000370956.4
SLCO1B3-SLCO1B7	ENST00000540229.1	c.728-5971A>C		intron_variant	Intron 6 of 15	2		ENSP00000441269.1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110141 AN: 151980 Hom.: 42509 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.779

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.724 AC: 110165 AN: 152100 Hom.: 42506 Cov.: 32 AF XY: 0.723 AC XY: 53794 AN XY: 74364

African (AFR) AF: 0.436 AC: 18065 AN: 41476

American (AMR) AF: 0.812 AC: 12407 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3085 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3697 AN: 5142

South Asian (SAS) AF: 0.900 AC: 4343 AN: 4826

European-Finnish (FIN) AF: 0.746 AC: 7900 AN: 10594

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 57987 AN: 67992

Other (OTH) AF: 0.778 AC: 1644 AN: 2112

Alfa AF: 0.751 Hom.: 5762

Bravo AF: 0.717

Asia WGS AF: 0.764 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.20
PhyloP100		-2.1
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: rs7953425; hg19: chr12-21022198;