12-21231448-G-C

Position:

• chr12-21231448-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.1865+6609G>C		intron_variant		ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1865+6609G>C		intron_variant		1	NM_006446.5	ENSP00000256958	P1

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

Gnomad4 AFR AF: 0.0818

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.137

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs11045884; hg19: chr12-21384382;