rs1424426

Positions:

• chr7-134458938-T-C
• chr7-134458938-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B1	NM_001628.4	c.66+59A>G		intron_variant		ENST00000285930.9	NP_001619.1
AKR1B1	NM_001346142.1	c.-367+184A>G		intron_variant			NP_001333071.1
AKR1B1	NR_144376.2	n.104+59A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9	c.66+59A>G		intron_variant		1	NM_001628.4	ENSP00000285930.3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78641 AN: 151832 Hom.: 21849 Cov.: 33

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

Gnomad4 AFR exome AF: 0.735

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.518 AC: 78737 AN: 151950 Hom.: 21892 Cov.: 33 AF XY: 0.512 AC XY: 38035 AN XY: 74288

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.500

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs1424426; hg19: chr7-134143690; COSMIC: COSV53649258;