rs3829310

Variant names:

• chr12-21139122-G-A
• rs3829310
• NM_006446.5:c.-61-2392G>A

Variant summary

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

The NM_006446.5(SLCO1B1):​c.-61-2392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,034 control chromosomes in the GnomAD database, including 53,103 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 0.81 (53103 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 3 publications found

Genes affected

SLCO1B1 (HGNC:10959): (solute carrier organic anion transporter family member 1B1) 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 numerous endogenous compounds including bilirubin, 17-beta-glucuronosyl estradiol and leukotriene C4. This protein is also involved in the removal of drug compounds such as statins, bromosulfophthalein and rifampin from the blood into the hepatocytes. Polymorphisms in the gene encoding this protein are associated with impaired transporter function. [provided by RefSeq, Mar 2009]

SLCO1B1 Gene-Disease associations (from GenCC):

• Rotor syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000257062 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.-61-2392G>A		intron_variant	Intron 1 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.-61-2392G>A		intron_variant	Intron 1 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123758 AN: 151916 Hom.: 53076 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.845

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

GnomAD4 genome AF: 0.815 AC: 123834 AN: 152034 Hom.: 53103 Cov.: 31 AF XY: 0.818 AC XY: 60790 AN XY: 74334

African (AFR) AF: 0.512 AC: 21167 AN: 41354

American (AMR) AF: 0.905 AC: 13836 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3272 AN: 3472

East Asian (EAS) AF: 0.859 AC: 4446 AN: 5174

South Asian (SAS) AF: 0.956 AC: 4615 AN: 4828

European-Finnish (FIN) AF: 0.910 AC: 9635 AN: 10592

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.940 AC: 63918 AN: 68010

Other (OTH) AF: 0.846 AC: 1787 AN: 2112

Alfa AF: 0.909 Hom.: 105042

Bravo AF: 0.798

Asia WGS AF: 0.889 AC: 3091 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-2.6
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: rs3829310; hg19: chr12-21292056;