NM_006446.5:c.85-3528G>A

Variant names:

• chr12-21169122-G-A
• rs11045813
• NM_006446.5:c.85-3528G>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.85-3528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,078 control chromosomes in the GnomAD database, including 1,246 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 (1246 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 8 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.85-3528G>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.85-3528G>A		intron_variant	Intron 2 of 14	1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*142-7654G>A		intron_variant	Intron 5 of 5	4		ENSP00000454306.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16873 AN: 151960 Hom.: 1247 Cov.: 32

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.111 AC: 16864 AN: 152078 Hom.: 1246 Cov.: 32 AF XY: 0.106 AC XY: 7886 AN XY: 74360

African (AFR) AF: 0.0384 AC: 1594 AN: 41514

American (AMR) AF: 0.102 AC: 1562 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5174

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4822

European-Finnish (FIN) AF: 0.104 AC: 1098 AN: 10564

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11016 AN: 67956

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.114 Hom.: 356

Bravo AF: 0.110

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.34
PhyloP100		-1.6
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: rs11045813; hg19: chr12-21322056;