Genetic Variant NM_001628.4:c.66+59A>G (chr7-134458938-T-C) – 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.66+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,550,482 control chromosomes in the GnomAD database, including 167,070 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 0.52 ( 21892 hom., cov: 33)

Exomes 𝑓: 0.45 ( 145178 hom. )

Consequence

AKR1B1
NM_001628.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.135

Publications

9 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 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.66+59A>G	intron	N/A	NP_001619.1	P15121
AKR1B1	NM_001346142.1		c.-367+184A>G	intron	N/A	NP_001333071.1
AKR1B1	NR_144376.2		n.104+59A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1B1	ENST00000285930.9	TSL:1 MANE Select	c.66+59A>G	intron	N/A	ENSP00000285930.3	P15121
AKR1B1	ENST00000465351.5	TSL:1	n.106+59A>G	intron	N/A
AKR1B1	ENST00000467829.1	TSL:1	n.163+184A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78641

AN:

151832

Hom.:

21849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.501

GnomAD4 exome

AF:

0.452

AC:

631517

AN:

1398532

Hom.:

145178

AF XY:

0.450

AC XY:

311708

AN XY:

692132

show subpopulations

African (AFR)

AF:

0.735

AC:

23540

AN:

32006

American (AMR)

AF:

0.442

AC:

16630

AN:

37666

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

9475

AN:

25180

East Asian (EAS)

AF:

0.514

AC:

18939

AN:

36838

South Asian (SAS)

AF:

0.460

AC:

36822

AN:

80010

European-Finnish (FIN)

AF:

0.370

AC:

17625

AN:

47694

Middle Eastern (MID)

AF:

0.395

AC:

1979

AN:

5016

European-Non Finnish (NFE)

AF:

0.446

AC:

479846

AN:

1076104

Other (OTH)

AF:

0.460

AC:

26661

AN:

58018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

18262

36525

54787

73050

91312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14688

29376

44064

58752

73440

<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:

0.518

AC:

78737

AN:

151950

Hom.:

21892

Cov.:

AF XY:

0.512

AC XY:

38035

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.732

AC:

30350

AN:

41490

American (AMR)

AF:

0.428

AC:

6536

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1350

AN:

3466

East Asian (EAS)

AF:

0.562

AC:

2862

AN:

5094

South Asian (SAS)

AF:

0.465

AC:

2247

AN:

4830

European-Finnish (FIN)

AF:

0.362

AC:

3830

AN:

10590

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.443

AC:

30046

AN:

67884

Other (OTH)

AF:

0.500

AC:

1053

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1863

3726

5590

7453

9316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.485

Hom.:

2325

Bravo

AF:

0.535

Asia WGS

AF:

0.512

AC:

1780

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.40

PhyloP100

-0.14

PromoterAI

0.034

Neutral

(source)

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