Genetic Variant AKR1E2:c.40-294G>A (chr10-4830381-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001040177.3(AKR1E2):c.40-294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 152,314 control chromosomes in the GnomAD database, including 74,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.99 ( 74229 hom., cov: 32)

Consequence

AKR1E2
NM_001040177.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.375

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

cataract
Inheritance: AR Classification: LIMITED Submitted by: G2P

AKR1E2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 10-4830381-G-A is Benign according to our data. Variant chr10-4830381-G-A is described in ClinVar as Benign. ClinVar VariationId is 1245332.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040177.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1E2	NM_001040177.3	MANE Select	c.40-294G>A	intron	N/A	NP_001035267.1	Q96JD6-1
AKR1E2	NM_001271021.2		c.40-294G>A	intron	N/A	NP_001257950.1	Q96JD6-2
AKR1E2	NM_001271025.2		c.40-294G>A	intron	N/A	NP_001257954.1	Q96JD6-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1E2	ENST00000298375.12	TSL:1 MANE Select	c.40-294G>A	intron	N/A	ENSP00000298375.7	Q96JD6-1
AKR1E2	ENST00000334019.4	TSL:1	c.40-294G>A	intron	N/A	ENSP00000335034.4	Q96JD6-2
AKR1E2	ENST00000532248.5	TSL:1	c.40-294G>A	intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes

AF:

0.987

AC:

150224

AN:

152196

Hom.:

74173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.993

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.991

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.987

AC:

150339

AN:

152314

Hom.:

74229

Cov.:

AF XY:

0.988

AC XY:

73569

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.956

AC:

39714

AN:

41552

American (AMR)

AF:

0.993

AC:

15204

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5184

AN:

5184

South Asian (SAS)

AF:

0.999

AC:

4815

AN:

4820

European-Finnish (FIN)

AF:

1.00

AC:

10616

AN:

10616

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68033

AN:

68042

Other (OTH)

AF:

0.991

AC:

2098

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

188

282

376

470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.995

Hom.:

16312

Bravo

AF:

0.986

Asia WGS

AF:

0.998

AC:

3470

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.26

(source)

DANN

Benign

0.76

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over