12-21141851-G-A

Position:

• chr12-21141851-G-A

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.84+193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 151,778 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.021 (99 hom., cov: 32)
• Consequence: SLCO1B1 NM_006446.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.335

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]

ENSG00000257062 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-21141851-G-A is Benign according to our data. Variant chr12-21141851-G-A is described in ClinVar as [Benign]. Clinvar id is 1282967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO1B1	NM_006446.5	c.84+193G>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.84+193G>A		intron_variant		1	NM_006446.5	ENSP00000256958.2
ENSG00000257062	ENST00000543498.5	n.*141+193G>A		intron_variant		4		ENSP00000454306.1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3260 AN: 151664 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00744

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.00831

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0202

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

GnomAD4 genome AF: 0.0215 AC: 3258 AN: 151778 Hom.: 99 Cov.: 32 AF XY: 0.0248 AC XY: 1838 AN XY: 74198

Gnomad4 AFR AF: 0.00299

Gnomad4 AMR AF: 0.00743

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.00831

Gnomad4 FIN AF: 0.0857

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0195

Alfa AF: 0.0184 Hom.: 32

Bravo AF: 0.0151

Asia WGS AF: 0.0530 AC: 183 AN: 3442

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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
DANN	Benign	0.68

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: rs4149021; hg19: chr12-21294785;