dbSNP rs759853: AKR1B1:n.79C>T (chr7-134459206-G-A) – 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.-451C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 979,370 control chromosomes in the GnomAD database, including 70,332 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 0.33 ( 8577 hom., cov: 33)

Exomes 𝑓: 0.38 ( 61755 hom. )

Consequence

AKR1B1
NM_001346142.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

Publications

81 publications found

Variant links:

COSMIC-nc: COSV53649543

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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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.-451C>T	5_prime_UTR	Exon 1 of 10	NP_001333071.1
AKR1B1	NM_001628.4	MANE Select	c.-144C>T	upstream_gene	N/A	NP_001619.1	P15121
AKR1B1	NR_144376.2		n.-106C>T	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
AKR1B1	ENST00000467829.1	TSL:1	n.79C>T	non_coding_transcript_exon	Exon 1 of 4
AKR1B1	ENST00000491741.5	TSL:1	n.79C>T	non_coding_transcript_exon	Exon 1 of 4
AKR1B1	ENST00000497983.5	TSL:4	n.47C>T	non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

49260

AN:

149092

Hom.:

8573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.243

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.338

GnomAD4 exome

AF:

0.384

AC:

318563

AN:

830154

Hom.:

61755

Cov.:

AF XY:

0.385

AC XY:

162169

AN XY:

421080

show subpopulations

African (AFR)

AF:

0.203

AC:

4187

AN:

20632

American (AMR)

AF:

0.346

AC:

10844

AN:

31350

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

6998

AN:

20130

East Asian (EAS)

AF:

0.188

AC:

6088

AN:

32326

South Asian (SAS)

AF:

0.393

AC:

22482

AN:

57242

European-Finnish (FIN)

AF:

0.357

AC:

12326

AN:

34504

Middle Eastern (MID)

AF:

0.319

AC:

905

AN:

2838

European-Non Finnish (NFE)

AF:

0.406

AC:

240788

AN:

592570

Other (OTH)

AF:

0.362

AC:

13945

AN:

38562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

10105

20210

30314

40419

50524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5704

11408

17112

22816

28520

<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:

0.330

AC:

49286

AN:

149216

Hom.:

8577

Cov.:

AF XY:

0.327

AC XY:

23852

AN XY:

72876

show subpopulations

African (AFR)

AF:

0.210

AC:

8670

AN:

41220

American (AMR)

AF:

0.329

AC:

4991

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1217

AN:

3432

East Asian (EAS)

AF:

0.197

AC:

988

AN:

5026

South Asian (SAS)

AF:

0.386

AC:

1646

AN:

4260

European-Finnish (FIN)

AF:

0.342

AC:

3584

AN:

10466

Middle Eastern (MID)

AF:

0.257

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.408

AC:

27076

AN:

66374

Other (OTH)

AF:

0.334

AC:

694

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1692

3384

5077

6769

8461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.357

Hom.:

12867

Bravo

AF:

0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.84

PhyloP100

-0.20

PromoterAI

0.072

Neutral

(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