rs11045823

Variant names:

• chr12-21180811-G-A
• rs11045823
• NM_006446.5:c.727+1791G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006446.5(SLCO1B1):​c.727+1791G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,138 control chromosomes in the GnomAD database, including 1,192 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 0.11 (1192 hom., cov: 33)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 6 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.727+1791G>A		intron_variant	Intron 7 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.727+1791G>A		intron_variant	Intron 7 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16498 AN: 152020 Hom.: 1193 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.0961

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.108 AC: 16495 AN: 152138 Hom.: 1192 Cov.: 33 AF XY: 0.104 AC XY: 7708 AN XY: 74378

African (AFR) AF: 0.0369 AC: 1534 AN: 41546

American (AMR) AF: 0.0958 AC: 1464 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3468

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5172

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1096 AN: 10576

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10808 AN: 67964

Other (OTH) AF: 0.107 AC: 225 AN: 2108

Alfa AF: 0.149 Hom.: 2101

Bravo AF: 0.108

Asia WGS AF: 0.0220 AC: 76 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	1.3
DANN	Benign	0.55
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11045823; hg19: chr12-21333745; COSMIC: COSV57016671; COSMIC: COSV57016671;