Genetic Variant AKR1B1:n.79C>A (chr7-134459206-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000467829.1(AKR1B1):n.79C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 831,652 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

AKR1B1
ENST00000467829.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

Publications

81 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AKR1B1	NM_001346142.1 link	c.-451C>A	5_prime_UTR_variant	Exon 1 of 10		NP_001333071.1
AKR1B1	NM_001628.4 link	c.-144C>A	upstream_gene_variant		ENST00000285930.9	NP_001619.1
AKR1B1	NR_144376.2 link	n.-106C>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9 link	c.-144C>A		upstream_gene_variant		1	NM_001628.4	ENSP00000285930.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000120

AC:

AN:

831652

Hom.:

Cov.:

AF XY:

0.00000237

AC XY:

AN XY:

421826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20664

American (AMR)

AF:

0.00

AC:

AN:

31370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20164

East Asian (EAS)

AF:

0.00

AC:

AN:

32336

South Asian (SAS)

AF:

0.0000175

AC:

AN:

57304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2838

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

593824

Other (OTH)

AF:

0.00

AC:

AN:

38620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

12867

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.70

PhyloP100

-0.20

PromoterAI

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over