Genetic Variant AKR1B1:n.163+11C>G (chr7-134459111-G-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_001346142.1(AKR1B1):c.-367+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 1,569,884 control chromosomes in the GnomAD database, including 8,873 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 0.15 ( 3863 hom., cov: 34)

Exomes 𝑓: 0.050 ( 5010 hom. )

Consequence

AKR1B1
NM_001346142.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

13 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 = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346142.1. 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_001346142.1		c.-367+11C>G	intron	N/A	NP_001333071.1
AKR1B1	NM_001628.4	MANE Select	c.-49C>G	upstream_gene	N/A	NP_001619.1	P15121
AKR1B1	NR_144376.2		n.-11C>G	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AKR1B1	ENST00000467829.1	TSL:1	n.163+11C>G	intron	N/A
AKR1B1	ENST00000491741.5	TSL:1	n.163+11C>G	intron	N/A
AKR1B1	ENST00000916181.1		c.-49C>G	5_prime_UTR	Exon 1 of 10	ENSP00000586240.1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22823

AN:

152092

Hom.:

3850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0731

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0744

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.135

GnomAD2 exomes

AF:

0.0767

AC:

13667

AN:

178124

AF XY:

0.0689

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.0583

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.0228

Gnomad NFE exome

AF:

0.0315

Gnomad OTH exome

AF:

0.0654

GnomAD4 exome

AF:

0.0500

AC:

70914

AN:

1417674

Hom.:

5010

Cov.:

AF XY:

0.0493

AC XY:

34566

AN XY:

701360

show subpopulations

African (AFR)

AF:

0.425

AC:

13753

AN:

32384

American (AMR)

AF:

0.0605

AC:

2331

AN:

38552

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

715

AN:

25314

East Asian (EAS)

AF:

0.214

AC:

7968

AN:

37286

South Asian (SAS)

AF:

0.0688

AC:

5550

AN:

80660

European-Finnish (FIN)

AF:

0.0224

AC:

1116

AN:

49848

Middle Eastern (MID)

AF:

0.0805

AC:

447

AN:

5552

European-Non Finnish (NFE)

AF:

0.0319

AC:

34742

AN:

1089348

Other (OTH)

AF:

0.0731

AC:

4292

AN:

58730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3323

6646

9969

13292

16615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1646

3292

4938

6584

8230

<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:

0.150

AC:

22875

AN:

152210

Hom.:

3863

Cov.:

AF XY:

0.147

AC XY:

10941

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.419

AC:

17416

AN:

41524

American (AMR)

AF:

0.0729

AC:

1115

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1137

AN:

5146

South Asian (SAS)

AF:

0.0742

AC:

358

AN:

4822

European-Finnish (FIN)

AF:

0.0218

AC:

231

AN:

10612

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0323

AC:

2199

AN:

68016

Other (OTH)

AF:

0.138

AC:

291

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

808

1616

2423

3231

4039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.0356

Hom.:

Bravo

AF:

0.167

Asia WGS

AF:

0.171

AC:

593

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

0.83

(source)

DANN

Benign

0.49

PhyloP100

-1.5

PromoterAI

-0.064

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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