rs976754

Positions:

• chr12-21162588-A-G

Variant summary

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

The NM_006446.5(SLCO1B1):​c.85-10062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 152,198 control chromosomes in the GnomAD database, including 972 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 0.091 (972 hom., cov: 33)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B1	NM_006446.5	c.85-10062A>G		intron_variant		ENST00000256958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.85-10062A>G		intron_variant		1	NM_006446.5	P1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13872 AN: 152082 Hom.: 970 Cov.: 33

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0890

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0972

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

GnomAD4 genome AF: 0.0912 AC: 13873 AN: 152198 Hom.: 972 Cov.: 33 AF XY: 0.0966 AC XY: 7186 AN XY: 74396

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0808 Hom.: 83

Bravo AF: 0.0868

Asia WGS AF: 0.214 AC: 740 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.72

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: rs976754; hg19: chr12-21315522;