Genetic Variant AKR1A1:c.*132A>T (chr1-45570088-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006066.4(AKR1A1):c.*132A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 917,850 control chromosomes in the GnomAD database, including 107,523 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 16877 hom., cov: 32)

Exomes 𝑓: 0.49 ( 90646 hom. )

Consequence

AKR1A1
NM_006066.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.519

Publications

10 publications found

Variant links:

COSMIC-nc: COSV61086540

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006066.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKR1A1	NM_153326.3	MANE Select	c.*132A>T	downstream_gene	N/A	NP_697021.1
AKR1A1	NM_001202413.2		c.*132A>T	downstream_gene	N/A	NP_001189342.1
AKR1A1	NM_001202414.2		c.*132A>T	downstream_gene	N/A	NP_001189343.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKR1A1	ENST00000351829.9	TSL:1 MANE Select	c.*132A>T	downstream_gene	N/A	ENSP00000312606.4
AKR1A1	ENST00000372070.7	TSL:1	c.*132A>T	downstream_gene	N/A	ENSP00000361140.3
AKR1A1	ENST00000863950.1		c.*132A>T	downstream_gene	N/A	ENSP00000534009.1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71320

AN:

151932

Hom.:

16892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.462

GnomAD4 exome

AF:

0.485

AC:

371629

AN:

765800

Hom.:

90646

Cov.:

AF XY:

0.485

AC XY:

192535

AN XY:

396888

show subpopulations

African (AFR)

AF:

0.423

AC:

8298

AN:

19624

American (AMR)

AF:

0.558

AC:

19473

AN:

34908

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

9241

AN:

18362

East Asian (EAS)

AF:

0.649

AC:

22355

AN:

34422

South Asian (SAS)

AF:

0.498

AC:

30973

AN:

62230

European-Finnish (FIN)

AF:

0.487

AC:

21419

AN:

44008

Middle Eastern (MID)

AF:

0.466

AC:

1333

AN:

2860

European-Non Finnish (NFE)

AF:

0.469

AC:

240693

AN:

512690

Other (OTH)

AF:

0.486

AC:

17844

AN:

36696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9280

18561

27841

37122

46402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4848

9696

14544

19392

24240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.469

AC:

71304

AN:

152050

Hom.:

16877

Cov.:

AF XY:

0.472

AC XY:

35059

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.425

AC:

17628

AN:

41462

American (AMR)

AF:

0.513

AC:

7834

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1761

AN:

3470

East Asian (EAS)

AF:

0.624

AC:

3225

AN:

5172

South Asian (SAS)

AF:

0.506

AC:

2437

AN:

4816

European-Finnish (FIN)

AF:

0.483

AC:

5105

AN:

10570

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.468

AC:

31789

AN:

67978

Other (OTH)

AF:

0.456

AC:

960

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1972

3944

5917

7889

9861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.312

Hom.:

762

Bravo

AF:

0.468

Asia WGS

AF:

0.537

AC:

1865

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over