Genetic Variant AKR1E2:c.40-207delT (chr10-4830459-GT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001040177.3(AKR1E2):c.40-207delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 151,076 control chromosomes in the GnomAD database, including 149 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 149 hom., cov: 32)

Consequence

AKR1E2
NM_001040177.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.616

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 -10 ACMG points.

BP6

Variant 10-4830459-GT-G is Benign according to our data. Variant chr10-4830459-GT-G is described in ClinVar as Benign. ClinVar VariationId is 1302864.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 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.40-207delT	intron	N/A	NP_001035267.1	Q96JD6-1
AKR1E2	NM_001271021.2		c.40-207delT	intron	N/A	NP_001257950.1	Q96JD6-2
AKR1E2	NM_001271025.2		c.40-207delT	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.40-215delT	intron	N/A	ENSP00000298375.7	Q96JD6-1
AKR1E2	ENST00000334019.4	TSL:1	c.40-215delT	intron	N/A	ENSP00000335034.4	Q96JD6-2
AKR1E2	ENST00000532248.5	TSL:1	c.40-215delT	intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5395

AN:

150962

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0223

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0497

Gnomad OTH

AF:

0.0376

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

GnomAD4 genome

AF:

0.0357

AC:

5392

AN:

151076

Hom.:

149

Cov.:

AF XY:

0.0340

AC XY:

2509

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.0118

AC:

485

AN:

41124

American (AMR)

AF:

0.0355

AC:

537

AN:

15146

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3462

East Asian (EAS)

AF:

0.115

AC:

594

AN:

5146

South Asian (SAS)

AF:

0.0223

AC:

106

AN:

4752

European-Finnish (FIN)

AF:

0.0161

AC:

166

AN:

10320

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0497

AC:

3370

AN:

67826

Other (OTH)

AF:

0.0377

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

268

536

805

1073

1341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0216

Hom.:

Bravo

AF:

0.0366

Asia WGS

AF:

0.0540

AC:

186

AN:

3476

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

PhyloP100

0.62

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