12-21231448-G-C

Variant names:

• chr12-21231448-G-C
• rs11045884
• NM_006446.5:c.1865+6609G>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+6609G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,968 control chromosomes in the GnomAD database, including 1,717 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 0.14 (1717 hom., cov: 31)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 4 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

LOC124903123 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 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.1865+6609G>C		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.1865+6609G>C		intron	N/A	ENSP00000256958.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20973 AN: 151850 Hom.: 1720 Cov.: 31

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.138 AC: 20973 AN: 151968 Hom.: 1717 Cov.: 31 AF XY: 0.133 AC XY: 9887 AN XY: 74282

African (AFR) AF: 0.0818 AC: 3389 AN: 41442

American (AMR) AF: 0.112 AC: 1714 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5166

South Asian (SAS) AF: 0.114 AC: 548 AN: 4810

European-Finnish (FIN) AF: 0.123 AC: 1304 AN: 10562

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12496 AN: 67952

Other (OTH) AF: 0.137 AC: 287 AN: 2102

Alfa AF: 0.149 Hom.: 238

Bravo AF: 0.137

Asia WGS AF: 0.0530 AC: 182 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.70
PhyloP100		0.17
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: rs11045884; hg19: chr12-21384382;