rs7489119

Positions:

• chr12-21152364-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006446.5(SLCO1B1):​c.84+10706C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 151,684 control chromosomes in the GnomAD database, including 103 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 0.029 (103 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.029 (4401/151684) while in subpopulation NFE AF= 0.0444 (3017/67876). AF 95% confidence interval is 0.0431. There are 103 homozygotes in gnomad4. There are 2117 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4401 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B1	NM_006446.5	c.84+10706C>A		intron_variant		ENST00000256958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.84+10706C>A		intron_variant		1	NM_006446.5	P1

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4405 AN: 151566 Hom.: 103 Cov.: 31

Gnomad AFR AF: 0.00733

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0254

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

GnomAD4 genome AF: 0.0290 AC: 4401 AN: 151684 Hom.: 103 Cov.: 31 AF XY: 0.0285 AC XY: 2117 AN XY: 74160

Gnomad4 AFR AF: 0.00731

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0393 Hom.: 180

Bravo AF: 0.0258

Asia WGS AF: 0.00433 AC: 15 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.36

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: rs7489119; hg19: chr12-21305298;