Genetic Variant AKR1A1:c.*278T>C (chr1-45567302-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000471651.1(AKR1A1):c.*278T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 368,810 control chromosomes in the GnomAD database, including 45,378 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 0.50 ( 18909 hom., cov: 32)

Exomes 𝑓: 0.49 ( 26469 hom. )

Consequence

AKR1A1
ENST00000471651.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Publications

25 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

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: ENST00000471651.1. 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.356+282T>C	intron	N/A	NP_697021.1
AKR1A1	NM_001202413.2		c.356+282T>C	intron	N/A	NP_001189342.1
AKR1A1	NM_001202414.2		c.356+282T>C	intron	N/A	NP_001189343.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKR1A1	ENST00000471651.1	TSL:1	c.*278T>C	3_prime_UTR	Exon 4 of 4	ENSP00000476713.1
AKR1A1	ENST00000351829.9	TSL:1 MANE Select	c.356+282T>C	intron	N/A	ENSP00000312606.4
AKR1A1	ENST00000372070.7	TSL:1	c.356+282T>C	intron	N/A	ENSP00000361140.3

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75578

AN:

151828

Hom.:

18920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.488

AC:

105819

AN:

216864

Hom.:

26469

Cov.:

AF XY:

0.488

AC XY:

54504

AN XY:

111576

show subpopulations

African (AFR)

AF:

0.511

AC:

3564

AN:

6970

American (AMR)

AF:

0.533

AC:

4326

AN:

8120

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

3723

AN:

7512

East Asian (EAS)

AF:

0.658

AC:

10365

AN:

15756

South Asian (SAS)

AF:

0.483

AC:

6940

AN:

14382

European-Finnish (FIN)

AF:

0.485

AC:

6702

AN:

13812

Middle Eastern (MID)

AF:

0.469

AC:

476

AN:

1014

European-Non Finnish (NFE)

AF:

0.465

AC:

63054

AN:

135532

Other (OTH)

AF:

0.484

AC:

6669

AN:

13766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2541

5082

7622

10163

12704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.497

AC:

75562

AN:

151946

Hom.:

18909

Cov.:

AF XY:

0.500

AC XY:

37112

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.523

AC:

21674

AN:

41452

American (AMR)

AF:

0.524

AC:

7989

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1753

AN:

3468

East Asian (EAS)

AF:

0.624

AC:

3206

AN:

5134

South Asian (SAS)

AF:

0.503

AC:

2428

AN:

4828

European-Finnish (FIN)

AF:

0.483

AC:

5097

AN:

10558

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31851

AN:

67940

Other (OTH)

AF:

0.471

AC:

992

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1933

3866

5800

7733

9666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.477

Hom.:

29292

Bravo

AF:

0.500

Asia WGS

AF:

0.546

AC:

1895

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

-0.0070

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -14

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