12-21176804-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_006446.5(SLCO1B1):c.388A>G(p.Asn130Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,504,300 control chromosomes in the GnomAD database, including 143,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23489 hom., cov: 32)

Exomes 𝑓: 0.41 ( 120456 hom. )

Consequence

SLCO1B1
NM_006446.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.275

Variant links:

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 links:

ENSG00000257062 (HGNC:):

ENSG00000257062 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity SO1B1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=1.6842818E-6).

BP6

Variant 12-21176804-A-G is Benign according to our data. Variant chr12-21176804-A-G is described in ClinVar as [Benign]. Clinvar id is 259983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-21176804-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1B1	NM_006446.5 link	c.388A>G	p.Asn130Asp	missense_variant	Exon 5 of 15	ENST00000256958.3	NP_006437.3	Q9Y6L6Q05CV5A0A024RAU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLCO1B1	ENST00000256958.3 link	c.388A>G	p.Asn130Asp	missense_variant	Exon 5 of 15	1	NM_006446.5	ENSP00000256958.2	Q9Y6L6
ENSG00000257062	ENST00000543498.5 link	n.*170A>G		non_coding_transcript_exon_variant	Exon 6 of 6	4		ENSP00000454306.1	H3BMA8
ENSG00000257062	ENST00000543498.5 link	n.*170A>G		3_prime_UTR_variant	Exon 6 of 6	4		ENSP00000454306.1	H3BMA8

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80757

AN:

151812

Hom.:

23449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.746

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.512

GnomAD3 exomes

AF:

0.474

AC:

118510

AN:

250172

Hom.:

29973

AF XY:

0.466

AC XY:

63100

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.450

Gnomad EAS exome

AF:

0.751

Gnomad SAS exome

AF:

0.476

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.406

AC:

548628

AN:

1352370

Hom.:

120456

Cov.:

AF XY:

0.407

AC XY:

275414

AN XY:

676626

show subpopulations

Gnomad4 AFR exome

AF:

0.782

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.466

Gnomad4 FIN exome

AF:

0.442

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.532

AC:

80854

AN:

151930

Hom.:

23489

Cov.:

AF XY:

0.535

AC XY:

39743

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.768

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.516

Gnomad4 FIN

AF:

0.455

Gnomad4 NFE

AF:

0.401

Gnomad4 OTH

AF:

0.514

Alfa

AF:

0.435

Hom.:

33750

Bravo

AF:

0.544

TwinsUK

AF:

0.403

AC:

1495

ALSPAC

AF:

0.397

AC:

1530

ESP6500AA

AF:

0.765

AC:

3365

ESP6500EA

AF:

0.404

AC:

3460

ExAC

AF:

0.479

AC:

58132

Asia WGS

AF:

0.656

AC:

2283

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rotor syndrome

Benign:4

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Gilbert syndrome

Benign:1

May 01, 2019

Difficult and Complicated Liver Diseases and Artificial Liver Center, Beijing You An Hospital, Capital Medical University

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.63

DANN

Benign

0.46

DEOGEN2

Benign

0.035

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.067

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.60

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

REVEL

Benign

0.023

Sift

Benign

0.45

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.023

MPC

0.010

ClinPred

0.0043

GERP RS

-2.6

Varity_R

0.051

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over