rs7489119

Variant names:

• chr12-21152364-C-A
• rs7489119
• NM_006446.5:c.84+10706C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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

ENSG00000257062 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 103 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.84+10706C>A		intron_variant	Intron 2 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.84+10706C>A		intron_variant	Intron 2 of 14	1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*141+10706C>A		intron_variant	Intron 5 of 5	4		ENSP00000454306.1

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

African (AFR) AF: 0.00731 AC: 303 AN: 41442

American (AMR) AF: 0.0183 AC: 278 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3464

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4816

European-Finnish (FIN) AF: 0.0553 AC: 574 AN: 10386

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0444 AC: 3017 AN: 67876

Other (OTH) AF: 0.0251 AC: 53 AN: 2110

Alfa AF: 0.0388 Hom.: 248

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
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

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: rs7489119; hg19: chr12-21305298;