rs11045879

Variant names:

• chr12-21229685-T-C
• rs11045879
• NM_006446.5:c.1865+4846T>C

Variant summary

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

The NM_006446.5(SLCO1B1):​c.1865+4846T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,080 control chromosomes in the GnomAD database, including 2,976 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 0.19 (2976 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 89 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.1865+4846T>C		intron_variant	Intron 14 of 14	ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1865+4846T>C		intron_variant	Intron 14 of 14	1	NM_006446.5	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28202 AN: 151964 Hom.: 2972 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.186 AC: 28226 AN: 152080 Hom.: 2976 Cov.: 32 AF XY: 0.195 AC XY: 14509 AN XY: 74328

African (AFR) AF: 0.159 AC: 6584 AN: 41520

American (AMR) AF: 0.180 AC: 2745 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2326 AN: 5168

South Asian (SAS) AF: 0.0883 AC: 426 AN: 4822

European-Finnish (FIN) AF: 0.321 AC: 3387 AN: 10544

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11634 AN: 67972

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.176 Hom.: 6519

Bravo AF: 0.177

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.4
DANN	Benign	0.50
PhyloP100		0.15
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: rs11045879; hg19: chr12-21382619;