Variant 12-21304500-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386879.1(SLCO1A2):c.516A>C(p.Glu172Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 1,611,832 control chromosomes in the GnomAD database, including 2,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.043 ( 200 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2517 hom. )

Consequence

SLCO1A2
NM_001386879.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

Variant links:

Genes affected

SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

SLCO1A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068627).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO1A2	NM_001386879.1 linkuse as main transcript	c.516A>C	p.Glu172Asp	missense_variant	6/15	ENST00000683939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO1A2	ENST00000683939.1 linkuse as main transcript	c.516A>C	p.Glu172Asp	missense_variant	6/15		NM_001386879.1	P1	P46721-1

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6546

AN:

152058

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0743

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.0469

GnomAD3 exomes

AF:

0.0450

AC:

11305

AN:

251144

Hom.:

357

AF XY:

0.0454

AC XY:

6157

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.0343

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.0795

Gnomad NFE exome

AF:

0.0622

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0553

AC:

80721

AN:

1459658

Hom.:

2517

Cov.:

AF XY:

0.0544

AC XY:

39499

AN XY:

726200

show subpopulations

Gnomad4 AFR exome

AF:

0.0167

Gnomad4 AMR exome

AF:

0.0296

Gnomad4 ASJ exome

AF:

0.0340

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.0821

Gnomad4 NFE exome

AF:

0.0620

Gnomad4 OTH exome

AF:

0.0473

GnomAD4 genome

AF:

0.0430

AC:

6544

AN:

152174

Hom.:

200

Cov.:

AF XY:

0.0425

AC XY:

3162

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0743

Gnomad4 NFE

AF:

0.0596

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0527

Hom.:

477

Bravo

AF:

0.0402

TwinsUK

AF:

0.0626

AC:

232

ALSPAC

AF:

0.0597

AC:

230

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.0558

AC:

480

ExAC

AF:

0.0455

AC:

5520

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0524

EpiControl

AF:

0.0527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Pathogenic

3.7

H;.

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;.

Vest4

0.48

MutPred

0.36

Gain of catalytic residue at L176 (P = 0);.;

MPC

0.24

ClinPred

0.058

GERP RS

3.6

Varity_R

0.86

gMVP

0.78

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over