12-21177088-G-A

Variant names:

• chr12-21177088-G-A
• rs4149046
• NM_006446.5:c.481+191G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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

ENSG00000257062 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1295257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 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.481+191G>A		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.481+191G>A		intron	N/A	ENSP00000256958.2
	ENSG00000257062	ENST00000543498.5	TSL:4	n.*454G>A		downstream_gene	N/A	ENSP00000454306.1

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

African (AFR) AF: 0.105 AC: 4359 AN: 41504

American (AMR) AF: 0.426 AC: 6502 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1304 AN: 5166

South Asian (SAS) AF: 0.450 AC: 2167 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4561 AN: 10544

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33044 AN: 67904

Other (OTH) AF: 0.381 AC: 801 AN: 2104

Alfa AF: 0.445 Hom.: 26309

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

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.46
PhyloP100		-0.84
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: rs4149046; hg19: chr12-21330022;