Genetic Variant AKR1B1:c.825+95A>C (chr7-134447203-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001628.4(AKR1B1):c.825+95A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,116,356 control chromosomes in the GnomAD database, including 287,064 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 0.71 ( 38439 hom., cov: 31)

Exomes 𝑓: 0.72 ( 248625 hom. )

Consequence

AKR1B1
NM_001628.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.110

Publications

7 publications found

Variant links:

Genes affected

AKR1B1 (HGNC:381): (aldo-keto reductase family 1 member B) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member catalyzes the reduction of a number of aldehydes, including the aldehyde form of glucose, and is thereby implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Multiple pseudogenes have been identified for this gene. The nomenclature system used by the HUGO Gene Nomenclature Committee to define human aldo-keto reductase family members is known to differ from that used by the Mouse Genome Informatics database. [provided by RefSeq, Feb 2009]

AKR1B1 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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001628.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1B1	NM_001628.4	MANE Select	c.825+95A>C	intron	N/A	NP_001619.1	P15121
AKR1B1	NM_001346142.1		c.393+95A>C	intron	N/A	NP_001333071.1
AKR1B1	NR_144376.2		n.1461+95A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1B1	ENST00000285930.9	TSL:1 MANE Select	c.825+95A>C	intron	N/A	ENSP00000285930.3	P15121
AKR1B1	ENST00000465351.5	TSL:1	n.1463+95A>C	intron	N/A
AKR1B1	ENST00000971768.1		c.825+95A>C	intron	N/A	ENSP00000641827.1

Frequencies

GnomAD3 genomes

AF:

0.708

AC:

107570

AN:

151954

Hom.:

38395

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.753

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.683

GnomAD4 exome

AF:

0.715

AC:

689598

AN:

964284

Hom.:

248625

AF XY:

0.712

AC XY:

354312

AN XY:

497770

show subpopulations

African (AFR)

AF:

0.691

AC:

16326

AN:

23616

American (AMR)

AF:

0.825

AC:

33377

AN:

40442

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

14172

AN:

22738

East Asian (EAS)

AF:

0.924

AC:

33572

AN:

36336

South Asian (SAS)

AF:

0.677

AC:

49740

AN:

73440

European-Finnish (FIN)

AF:

0.757

AC:

34892

AN:

46072

Middle Eastern (MID)

AF:

0.517

AC:

1664

AN:

3220

European-Non Finnish (NFE)

AF:

0.704

AC:

475094

AN:

674526

Other (OTH)

AF:

0.701

AC:

30761

AN:

43894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

11235

22470

33706

44941

56176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9390

18780

28170

37560

46950

<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:

0.708

AC:

107669

AN:

152072

Hom.:

38439

Cov.:

AF XY:

0.713

AC XY:

52949

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.692

AC:

28706

AN:

41474

American (AMR)

AF:

0.753

AC:

11516

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2162

AN:

3472

East Asian (EAS)

AF:

0.916

AC:

4710

AN:

5142

South Asian (SAS)

AF:

0.677

AC:

3256

AN:

4806

European-Finnish (FIN)

AF:

0.759

AC:

8048

AN:

10598

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47151

AN:

67976

Other (OTH)

AF:

0.683

AC:

1442

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1628

3257

4885

6514

8142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.701

Hom.:

71534

Bravo

AF:

0.709

Asia WGS

AF:

0.783

AC:

2723

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.5

(source)

DANN

Benign

0.76

PhyloP100

-0.11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over