rs11045821

Variant names:

• chr12-21179489-G-A
• rs11045821
• NM_006446.5:c.727+469G>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+469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,102 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: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 13 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 = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006446.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	NM_006446.5	MANE Select	c.727+469G>A		intron	N/A	NP_006437.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO1B1	ENST00000256958.3	TSL:1 MANE Select	c.727+469G>A		intron	N/A	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16678 AN: 151984 Hom.: 1193 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.105

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: 0.110 AC: 16676 AN: 152102 Hom.: 1192 Cov.: 32 AF XY: 0.105 AC XY: 7795 AN XY: 74350

African (AFR) AF: 0.0410 AC: 1703 AN: 41538

American (AMR) AF: 0.0963 AC: 1470 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 734 AN: 3466

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5170

South Asian (SAS) AF: 0.0437 AC: 211 AN: 4828

European-Finnish (FIN) AF: 0.105 AC: 1111 AN: 10572

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

European-Non Finnish (NFE) AF: 0.159 AC: 10795 AN: 67948

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

Alfa AF: 0.139 Hom.: 4568

Bravo AF: 0.109

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.45
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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: rs11045821; hg19: chr12-21332423; COSMIC: COSV57016667; COSMIC: COSV57016667;