12-21182256-C-G

Variant names:

• chr12-21182256-C-G
• rs1564370
• NM_006446.5:c.727+3236C>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.727+3236C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,898 control chromosomes in the GnomAD database, including 12,812 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 0.37 (12812 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.727+3236C>G		intron_variant	Intron 7 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.727+3236C>G		intron_variant	Intron 7 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56596 AN: 151778 Hom.: 12808 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.373 AC: 56598 AN: 151898 Hom.: 12812 Cov.: 31 AF XY: 0.374 AC XY: 27730 AN XY: 74210

African (AFR) AF: 0.109 AC: 4520 AN: 41494

American (AMR) AF: 0.458 AC: 6975 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3466

East Asian (EAS) AF: 0.253 AC: 1296 AN: 5132

South Asian (SAS) AF: 0.546 AC: 2624 AN: 4810

European-Finnish (FIN) AF: 0.440 AC: 4620 AN: 10510

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.498 AC: 33816 AN: 67938

Other (OTH) AF: 0.385 AC: 812 AN: 2108

Alfa AF: 0.431 Hom.: 1924

Bravo AF: 0.359

Asia WGS AF: 0.359 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		0.25
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: rs1564370; hg19: chr12-21335190;