Variant 10-4833399-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001040177.3(AKR1E2):c.257A>G(p.Lys86Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 1,614,026 control chromosomes in the GnomAD database, including 1,816 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.035 ( 149 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1667 hom. )

Consequence

AKR1E2
NM_001040177.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.683

Variant links:

Genes affected

AKR1E2 (HGNC:23437): (aldo-keto reductase family 1 member E2) The protein encoded by this gene is a member of the aldo-keto reductase superfamily. Members in this family are characterized by their structure (evolutionarily highly conserved TIM barrel) and function (NAD(P)H-dependent oxido-reduction of carbonyl groups). Transcripts of this gene have been reported in specimens of human testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

AKR1E2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043099523).

BP6

Variant 10-4833399-A-G is Benign according to our data. Variant chr10-4833399-A-G is described in ClinVar as [Benign]. Clinvar id is 1296595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3 linkuse as main transcript	c.257A>G	p.Lys86Arg	missense_variant	3/10	ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12 linkuse as main transcript	c.257A>G	p.Lys86Arg	missense_variant	3/10	1	NM_001040177.3	P1	Q96JD6-1

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5303

AN:

152158

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00975

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0399

AC:

10041

AN:

251440

Hom.:

303

AF XY:

0.0396

AC XY:

5376

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.0170

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0433

AC:

63339

AN:

1461750

Hom.:

1667

Cov.:

AF XY:

0.0428

AC XY:

31154

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00702

Gnomad4 AMR exome

AF:

0.0315

Gnomad4 ASJ exome

AF:

0.0155

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.0171

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.0465

Gnomad4 OTH exome

AF:

0.0364

GnomAD4 genome

AF:

0.0348

AC:

5300

AN:

152276

Hom.:

149

Cov.:

AF XY:

0.0331

AC XY:

2466

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00972

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0218

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.0496

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0452

Hom.:

388

Bravo

AF:

0.0360

TwinsUK

AF:

0.0480

AC:

178

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.0451

AC:

388

ExAC

AF:

0.0408

AC:

4950

Asia WGS

AF:

0.0540

AC:

187

AN:

3478

EpiCase

AF:

0.0457

EpiControl

AF:

0.0485

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.84

DANN

Benign

0.63

DEOGEN2

Benign

0.019

T;T;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.66

T;T;T;T;T

MetaRNN

Benign

0.0043

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.71

.;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.21

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T

Polyphen

0.0010, 0.0

.;B;B;B;B

Vest4

0.032, 0.031, 0.034

MPC

0.063

ClinPred

0.0065

GERP RS

-6.8

Varity_R

0.054

gMVP

0.34

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over