chr12-21141359-T-G

Position:

• chr12-21141359-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006446.5(SLCO1B1):​c.-61-155T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 151,858 control chromosomes in the GnomAD database, including 61,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.90 (61904 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-21141359-T-G is Benign according to our data. Variant chr12-21141359-T-G is described in ClinVar as [Benign]. Clinvar id is 1247535.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-21141359-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B1	NM_006446.5	c.-61-155T>G		intron_variant		ENST00000256958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.-61-155T>G		intron_variant		1	NM_006446.5	P1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136683 AN: 151740 Hom.: 61861 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.901 AC: 136787 AN: 151858 Hom.: 61904 Cov.: 32 AF XY: 0.901 AC XY: 66879 AN XY: 74236

Gnomad4 AFR AF: 0.805

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.910

Alfa AF: 0.937 Hom.: 134246

Bravo AF: 0.898

Asia WGS AF: 0.935 AC: 3236 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.45

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: rs2010668; hg19: chr12-21294293; COSMIC: COSV57007129;