12-21175490-G-C

Variant names:

• chr12-21175490-G-C
• rs4149040
• NM_006446.5:c.359+781G>C

Variant summary

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

The NM_006446.5(SLCO1B1):​c.359+781G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,968 control chromosomes in the GnomAD database, including 21,597 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 0.51 (21597 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.359+781G>C		intron_variant	Intron 4 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.359+781G>C		intron_variant	Intron 4 of 14	1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*142-1286G>C		intron_variant	Intron 5 of 5	4		ENSP00000454306.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77972 AN: 151852 Hom.: 21561 Cov.: 32

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.514 AC: 78056 AN: 151968 Hom.: 21597 Cov.: 32 AF XY: 0.515 AC XY: 38282 AN XY: 74290

African (AFR) AF: 0.717 AC: 29725 AN: 41478

American (AMR) AF: 0.463 AC: 7067 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1584 AN: 3466

East Asian (EAS) AF: 0.745 AC: 3855 AN: 5172

South Asian (SAS) AF: 0.401 AC: 1934 AN: 4820

European-Finnish (FIN) AF: 0.455 AC: 4803 AN: 10556

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27256 AN: 67916

Other (OTH) AF: 0.508 AC: 1071 AN: 2108

Alfa AF: 0.331 Hom.: 1055

Bravo AF: 0.526

Asia WGS AF: 0.607 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.80
DANN	Benign	0.32
PhyloP100		-0.73
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: rs4149040; hg19: chr12-21328424;