12-21164876-A-G

Position:

• chr12-21164876-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006446.5(SLCO1B1):​c.85-7774A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 476,994 control chromosomes in the GnomAD database, including 152,317 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 0.78 (46671 hom., cov: 32)
  • Exomes 𝑓: 0.80 (105646 hom.)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.85-7774A>G		intron_variant		ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.85-7774A>G		intron_variant		1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*142-11900A>G		intron_variant		4		ENSP00000454306.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118869 AN: 151944 Hom.: 46628 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.770

GnomAD3 exomes AF: 0.800 AC: 136478 AN: 170684 Hom.: 54874 AF XY: 0.805 AC XY: 75079 AN XY: 93244

Gnomad AFR exome AF: 0.764

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.807

Gnomad EAS exome AF: 0.862

Gnomad SAS exome AF: 0.917

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.804 AC: 261097 AN: 324932 Hom.: 105646 Cov.: 0 AF XY: 0.814 AC XY: 151067 AN XY: 185592

Gnomad4 AFR exome AF: 0.771

Gnomad4 AMR exome AF: 0.805

Gnomad4 ASJ exome AF: 0.806

Gnomad4 EAS exome AF: 0.857

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.696

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.782 AC: 118970 AN: 152062 Hom.: 46671 Cov.: 32 AF XY: 0.782 AC XY: 58123 AN XY: 74356

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.773

Alfa AF: 0.786 Hom.: 37260

Bravo AF: 0.787

Asia WGS AF: 0.888 AC: 3085 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.52

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: rs4149033; hg19: chr12-21317810;