rs4149032

Positions:

• chr12-21164857-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000257062 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.85-7793C>T		intron_variant		ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.85-7793C>T		intron_variant		1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*142-11919C>T		intron_variant		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

GnomAD3 exomes AF: 0.373 AC: 67808 AN: 181732 Hom.: 13729 AF XY: 0.369 AC XY: 36706 AN XY: 99430

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 SAS exome AF: 0.423

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

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.542

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.370

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

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.418

Alfa AF: 0.358 Hom.: 23880

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

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: rs4149032; hg19: chr12-21317791; COSMIC: COSV57009021;