7-134447203-T-G

Variant names:

• chr7-134447203-T-G
• rs2259458
• NM_001628.4:c.825+95A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKR1B1	NM_001628.4	c.825+95A>C		intron_variant	Intron 8 of 9	ENST00000285930.9	NP_001619.1
AKR1B1	NM_001346142.1	c.393+95A>C		intron_variant	Intron 8 of 9		NP_001333071.1
AKR1B1	NR_144376.2	n.1461+95A>C		intron_variant	Intron 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000285930.9	c.825+95A>C		intron_variant	Intron 8 of 9	1	NM_001628.4	ENSP00000285930.3
AKR1B1	ENST00000465351.5	n.1463+95A>C		intron_variant	Intron 7 of 8	1
AKR1B1	ENST00000434222.5	n.*552+95A>C		intron_variant	Intron 8 of 9	5		ENSP00000414399.1
AKR1B1	ENST00000467251.1	n.129+95A>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.691 AC: 16326 AN: 23616

American (AMR) AF: 0.825 AC: 33377 AN: 40442

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 14172 AN: 22738

East Asian (EAS) AF: 0.924 AC: 33572 AN: 36336

South Asian (SAS) AF: 0.677 AC: 49740 AN: 73440

European-Finnish (FIN) AF: 0.757 AC: 34892 AN: 46072

Middle Eastern (MID) AF: 0.517 AC: 1664 AN: 3220

European-Non Finnish (NFE) AF: 0.704 AC: 475094 AN: 674526

Other (OTH) AF: 0.701 AC: 30761 AN: 43894

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

African (AFR) AF: 0.692 AC: 28706 AN: 41474

American (AMR) AF: 0.753 AC: 11516 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4710 AN: 5142

South Asian (SAS) AF: 0.677 AC: 3256 AN: 4806

European-Finnish (FIN) AF: 0.759 AC: 8048 AN: 10598

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47151 AN: 67976

Other (OTH) AF: 0.683 AC: 1442 AN: 2110

Alfa AF: 0.701 Hom.: 71534

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2259458; hg19: chr7-134131955;