Genetic Variant AKR1A1:p.Gly51Ser (chr1-45566635-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153326.3(AKR1A1):c.151G>A(p.Gly51Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00884 in 1,614,224 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0068 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 88 hom. )

Consequence

AKR1A1
NM_153326.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

AKR1A1 (HGNC:380): (aldo-keto reductase family 1 member A1) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member, also known as aldehyde reductase, is involved in the reduction of biogenic and xenobiotic aldehydes and is present in virtually every tissue. Multiple alternatively spliced transcript variants of this gene exist, all encoding the same protein. [provided by RefSeq, Jan 2011]

AKR1A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010595292).

BP6

Variant 1-45566635-G-A is Benign according to our data. Variant chr1-45566635-G-A is described in ClinVar as [Benign]. Clinvar id is 775053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1A1	NM_153326.3 link	c.151G>A	p.Gly51Ser	missense_variant	Exon 3 of 9	ENST00000351829.9	NP_697021.1	P14550V9HWI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1A1	ENST00000351829.9 link	c.151G>A	p.Gly51Ser	missense_variant	Exon 3 of 9	1	NM_153326.3	ENSP00000312606.4		P14550
AKR1A1	ENST00000481885.5 link	c.151G>A	p.Gly51Ser	missense_variant	Exon 3 of 5	3		ENSP00000476978.1		V9GYP9

Frequencies

GnomAD3 genomes

AF:

0.00682

AC:

1038

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00688

AC:

1730

AN:

251444

Hom.:

AF XY:

0.00695

AC XY:

945

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00523

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00415

Gnomad FIN exome

AF:

0.00735

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00831

GnomAD4 exome

AF:

0.00905

AC:

13226

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00894

AC XY:

6500

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00550

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00428

Gnomad4 FIN exome

AF:

0.00783

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.00732

GnomAD4 genome

AF:

0.00682

AC:

1039

AN:

152346

Hom.:

Cov.:

AF XY:

0.00635

AC XY:

473

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00947

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00810

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00898

Hom.:

Bravo

AF:

0.00641

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00988

AC:

ExAC

AF:

0.00707

AC:

858

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00966

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T;.;T;T;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

.;D;D;D;.;D

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.7

M;M;.;.;M;.

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.9

D;.;D;.;D;.

REVEL

Benign

0.16

Sift

Benign

0.22

T;.;T;.;T;.

Sift4G

Benign

0.35

T;T;T;T;T;T

Polyphen

0.075

B;B;.;.;B;.

Vest4

0.14

MVP

0.56

MPC

0.067

ClinPred

0.034

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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