rs4149032

Variant names:

• chr12-21164857-C-T
• rs4149032
• NM_006446.5:c.85-7793C>T

Variant summary

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

The NM_006446.5(SLCO1B1):​c.85-7793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 485,758 control chromosomes in the GnomAD database, including 40,437 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 0.45 (16936 hom., cov: 32)
  • Exomes 𝑓: 0.36 (23501 hom.)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 60 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.85-7793C>T		intron_variant	Intron 2 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.85-7793C>T		intron_variant	Intron 2 of 14	1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*142-11919C>T		intron_variant	Intron 5 of 5	4		ENSP00000454306.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67715 AN: 151888 Hom.: 16914 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.416

GnomAD2 exomes AF: 0.373 AC: 67808 AN: 181732 AF XY: 0.369

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.544

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.357

GnomAD4 exome AF: 0.364 AC: 121488 AN: 333752 Hom.: 23501 Cov.: 0 AF XY: 0.367 AC XY: 69887 AN XY: 190574

African (AFR) AF: 0.678 AC: 6562 AN: 9676

American (AMR) AF: 0.342 AC: 10554 AN: 30904

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 4047 AN: 10936

East Asian (EAS) AF: 0.542 AC: 6626 AN: 12220

South Asian (SAS) AF: 0.427 AC: 26403 AN: 61858

European-Finnish (FIN) AF: 0.291 AC: 4366 AN: 15018

Middle Eastern (MID) AF: 0.339 AC: 940 AN: 2772

European-Non Finnish (NFE) AF: 0.322 AC: 56323 AN: 175052

Other (OTH) AF: 0.370 AC: 5667 AN: 15316

GnomAD4 genome AF: 0.446 AC: 67793 AN: 152006 Hom.: 16936 Cov.: 32 AF XY: 0.444 AC XY: 32981 AN XY: 74290

African (AFR) AF: 0.676 AC: 28025 AN: 41468

American (AMR) AF: 0.389 AC: 5937 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2947 AN: 5170

South Asian (SAS) AF: 0.477 AC: 2296 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3090 AN: 10544

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22619 AN: 67958

Other (OTH) AF: 0.418 AC: 885 AN: 2116

Alfa AF: 0.370 Hom.: 52422

Bravo AF: 0.463

Asia WGS AF: 0.556 AC: 1932 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.23
PhyloP100		-0.99
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: rs4149032; hg19: chr12-21317791; COSMIC: COSV57009021;