rs4149046

Positions:

• chr12-21177088-G-A
• chr12-21177088-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.481+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,966 control chromosomes in the GnomAD database, including 11,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.36 (11918 hom., cov: 33)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.843

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=-0.99).
• BP6: Variant 12-21177088-G-A is Benign according to our data. Variant chr12-21177088-G-A is described in ClinVar as [Benign]. Clinvar id is 1295257.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-21177088-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.481+191G>A		intron_variant		ENST00000256958.3	NP_006437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO1B1	ENST00000256958.3	c.481+191G>A		intron_variant		1	NM_006446.5	ENSP00000256958	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54688 AN: 151848 Hom.: 11916 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.360 AC: 54694 AN: 151966 Hom.: 11918 Cov.: 33 AF XY: 0.360 AC XY: 26700 AN XY: 74228

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.381

Alfa AF: 0.455 Hom.: 21253

Bravo AF: 0.348

Asia WGS AF: 0.316 AC: 1097 AN: 3478

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

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.46

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: rs4149046; hg19: chr12-21330022;