Genetic Variant AKR1E2:c.40-311C>G (chr10-4830364-C-G) – 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.40-311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,170 control chromosomes in the GnomAD database, including 3,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3363 hom., cov: 33)

Consequence

AKR1E2
NM_001040177.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.471

Publications

4 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=-0.76).

BP6

Variant 10-4830364-C-G is Benign according to our data. Variant chr10-4830364-C-G is described in ClinVar as Benign. ClinVar VariationId is 1239771.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 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.40-311C>G	intron	N/A	NP_001035267.1	Q96JD6-1
AKR1E2	NM_001271021.2		c.40-311C>G	intron	N/A	NP_001257950.1	Q96JD6-2
AKR1E2	NM_001271025.2		c.40-311C>G	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.40-311C>G	intron	N/A	ENSP00000298375.7	Q96JD6-1
AKR1E2	ENST00000334019.4	TSL:1	c.40-311C>G	intron	N/A	ENSP00000335034.4	Q96JD6-2
AKR1E2	ENST00000532248.5	TSL:1	c.40-311C>G	intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31069

AN:

152052

Hom.:

3367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.230

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

GnomAD4 genome

AF:

0.204

AC:

31064

AN:

152170

Hom.:

3363

Cov.:

AF XY:

0.200

AC XY:

14855

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.181

AC:

7507

AN:

41502

American (AMR)

AF:

0.193

AC:

2946

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1116

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

565

AN:

5174

South Asian (SAS)

AF:

0.198

AC:

954

AN:

4820

European-Finnish (FIN)

AF:

0.158

AC:

1675

AN:

10588

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15491

AN:

68006

Other (OTH)

AF:

0.232

AC:

490

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1274

2549

3823

5098

6372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.200

Hom.:

394

Bravo

AF:

0.207

Asia WGS

AF:

0.156

AC:

541

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

-0.76

CADD

Benign

1.3

(source)

DANN

Benign

0.73

PhyloP100

-0.47

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