chr12-21183129-C-T

Position:

• chr12-21183129-C-T

Variant summary

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

The ENST00000256958.3(SLCO1B1):​c.727+4109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,110 control chromosomes in the GnomAD database, including 38,083 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 0.70 (38083 hom., cov: 34)
• Consequence: SLCO1B1 ENST00000256958.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.727+4109C>T		intron_variant		ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.727+4109C>T		intron_variant		1	NM_006446.5	ENSP00000256958	P1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106163 AN: 151992 Hom.: 38069 Cov.: 34

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.698 AC: 106223 AN: 152110 Hom.: 38083 Cov.: 34 AF XY: 0.695 AC XY: 51656 AN XY: 74358

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.702

Alfa AF: 0.730 Hom.: 6931

Bravo AF: 0.696

Asia WGS AF: 0.685 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.62

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: rs2900476; hg19: chr12-21336063;