rs4149058

Variant names:

• chr12-21180280-A-G
• rs4149058
• NM_006446.5:c.727+1260A>G

Variant summary

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

The NM_006446.5(SLCO1B1):​c.727+1260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,920 control chromosomes in the GnomAD database, including 7,697 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 0.30 (7697 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 10 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.727+1260A>G		intron_variant	Intron 7 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.727+1260A>G		intron_variant	Intron 7 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46110 AN: 151804 Hom.: 7691 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.304 AC: 46153 AN: 151920 Hom.: 7697 Cov.: 32 AF XY: 0.309 AC XY: 22924 AN XY: 74274

African (AFR) AF: 0.419 AC: 17356 AN: 41422

American (AMR) AF: 0.246 AC: 3759 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2552 AN: 5152

South Asian (SAS) AF: 0.167 AC: 807 AN: 4822

European-Finnish (FIN) AF: 0.358 AC: 3774 AN: 10548

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16105 AN: 67936

Other (OTH) AF: 0.300 AC: 634 AN: 2110

Alfa AF: 0.250 Hom.: 8545

Bravo AF: 0.302

Asia WGS AF: 0.331 AC: 1149 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		-0.18
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: rs4149058; hg19: chr12-21333214;