12-21164876-A-G

Variant names:

• chr12-21164876-A-G
• rs4149033
• NM_006446.5:c.85-7774A>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.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
• Publications: 20 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=-0.97).
• 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 rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.85-7774A>G		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.85-7774A>G		intron_variant	Intron 2 of 14	1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*142-11900A>G		intron_variant	Intron 5 of 5	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

GnomAD2 exomes AF: 0.800 AC: 136478 AN: 170684 AF XY: 0.805

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 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

African (AFR) AF: 0.771 AC: 7104 AN: 9216

American (AMR) AF: 0.805 AC: 23705 AN: 29458

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 8694 AN: 10784

East Asian (EAS) AF: 0.857 AC: 10127 AN: 11810

South Asian (SAS) AF: 0.921 AC: 55886 AN: 60708

European-Finnish (FIN) AF: 0.696 AC: 10083 AN: 14480

Middle Eastern (MID) AF: 0.749 AC: 2067 AN: 2760

European-Non Finnish (NFE) AF: 0.771 AC: 131672 AN: 170694

Other (OTH) AF: 0.783 AC: 11759 AN: 15022

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

African (AFR) AF: 0.781 AC: 32408 AN: 41474

American (AMR) AF: 0.784 AC: 11972 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2828 AN: 3470

East Asian (EAS) AF: 0.870 AC: 4500 AN: 5174

South Asian (SAS) AF: 0.927 AC: 4474 AN: 4826

European-Finnish (FIN) AF: 0.693 AC: 7334 AN: 10578

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52852 AN: 67962

Other (OTH) AF: 0.773 AC: 1632 AN: 2110

Alfa AF: 0.784 Hom.: 52401

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
PhyloP100		-0.60
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: rs4149033; hg19: chr12-21317810;