rs4149081

Variant names:

• chr12-21225087-G-A
• rs4149081
• NM_006446.5:c.1865+248G>A

Variant summary

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

The NM_006446.5(SLCO1B1):​c.1865+248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,784 control chromosomes in the GnomAD database, including 2,980 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 0.19 (2980 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.1865+248G>A		intron_variant	Intron 14 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1865+248G>A		intron_variant	Intron 14 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28170 AN: 151668 Hom.: 2976 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0672

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.186 AC: 28195 AN: 151784 Hom.: 2980 Cov.: 32 AF XY: 0.196 AC XY: 14499 AN XY: 74132

African (AFR) AF: 0.159 AC: 6571 AN: 41444

American (AMR) AF: 0.180 AC: 2742 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2325 AN: 5154

South Asian (SAS) AF: 0.0887 AC: 427 AN: 4816

European-Finnish (FIN) AF: 0.324 AC: 3390 AN: 10468

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11616 AN: 67874

Other (OTH) AF: 0.194 AC: 409 AN: 2110

Alfa AF: 0.176 Hom.: 9072

Bravo AF: 0.176

Asia WGS AF: 0.259 AC: 896 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.61
PhyloP100		0.39
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: rs4149081; hg19: chr12-21378021;