7-134447203-T-G

Position:

• chr7-134447203-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.825+95A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,116,356 control chromosomes in the GnomAD database, including 287,064 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 0.71 (38439 hom., cov: 31)
  • Exomes 𝑓: 0.72 (248625 hom.)
• Consequence: AKR1B1 NM_001628.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B1	NM_001628.4	c.825+95A>C		intron_variant		ENST00000285930.9	NP_001619.1
AKR1B1	NM_001346142.1	c.393+95A>C		intron_variant			NP_001333071.1
AKR1B1	NR_144376.2	n.1461+95A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9	c.825+95A>C		intron_variant		1	NM_001628.4	ENSP00000285930.3
AKR1B1	ENST00000465351.5	n.1463+95A>C		intron_variant		1
AKR1B1	ENST00000434222.5	n.*552+95A>C		intron_variant		5		ENSP00000414399.1
AKR1B1	ENST00000467251.1	n.129+95A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107570 AN: 151954 Hom.: 38395 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.715 AC: 689598 AN: 964284 Hom.: 248625 AF XY: 0.712 AC XY: 354312 AN XY: 497770

Gnomad4 AFR exome AF: 0.691

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.924

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.757

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.708 AC: 107669 AN: 152072 Hom.: 38439 Cov.: 31 AF XY: 0.713 AC XY: 52949 AN XY: 74314

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.683

Alfa AF: 0.696 Hom.: 19576

Bravo AF: 0.709

Asia WGS AF: 0.783 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.76

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: rs2259458; hg19: chr7-134131955;