12-21224625-G-C

Position:

• chr12-21224625-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006446.5(SLCO1B1):​c.1748-97G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 797,010 control chromosomes in the GnomAD database, including 16,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2982 hom., cov: 32)
  • Exomes 𝑓: 0.19 (13442 hom.)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.59

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 12-21224625-G-C is Benign according to our data. Variant chr12-21224625-G-C is described in ClinVar as [Benign]. Clinvar id is 1295279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1B1	NM_006446.5	c.1748-97G>C		intron_variant		ENST00000256958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.1748-97G>C		intron_variant		1	NM_006446.5	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28193 AN: 151782 Hom.: 2979 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.188 AC: 121190 AN: 645110 Hom.: 13442 AF XY: 0.181 AC XY: 62942 AN XY: 347714

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.0771

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.186 AC: 28213 AN: 151900 Hom.: 2982 Cov.: 32 AF XY: 0.196 AC XY: 14513 AN XY: 74224

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.194

Alfa AF: 0.181 Hom.: 348

Bravo AF: 0.176

Asia WGS AF: 0.259 AC: 897 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.045
DANN	Benign	0.54

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: rs4149080; hg19: chr12-21377559;