rs7953425

chr12-20869264-A-Cchr12-20869264-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SLCO1B3	NM_019844.4	c.728-5971A>C		intron_variant		ENST00000381545.8
SLCO1B3-SLCO1B7	NM_001371097.1	c.728-5971A>C		intron_variant
SLCO1B3	NM_001349920.2	c.644-5971A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B3	ENST00000381545.8	c.728-5971A>C		intron_variant		2	NM_019844.4	P1
SLCO1B3	ENST00000261196.6	c.728-5971A>C		intron_variant		1		P1
SLCO1B3	ENST00000540853.5	c.728-5971A>C		intron_variant		1
SLCO1B3	ENST00000544370.1	c.200-5971A>C		intron_variant		5

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

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.778

Alfa AF: 0.762 Hom.: 5681

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

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: rs7953425; hg19: chr12-21022198;