rs759853

Positions:

• chr7-134459206-G-A
• chr7-134459206-G-T

Variant summary

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

The ENST00000467829.1(AKR1B1):​n.79C>T 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 0.376 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 ENST00000467829.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1B1	NM_001346142.1	c.-451C>T		5_prime_UTR_variant	1/10		NP_001333071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1B1	ENST00000467829.1	n.79C>T		non_coding_transcript_exon_variant	1/4	1
AKR1B1	ENST00000491741.5	n.79C>T		non_coding_transcript_exon_variant	1/4	1
AKR1B1	ENST00000497983.5	n.47C>T		non_coding_transcript_exon_variant	1/5	4
AKR1B1	ENST00000487438.5			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49260 AN: 149092 Hom.: 8573 Cov.: 33

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.: 11 AF XY: 0.385 AC XY: 162169 AN XY: 421080

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.362

GnomAD4 genome AF: 0.330 AC: 49286 AN: 149216 Hom.: 8577 Cov.: 33 AF XY: 0.327 AC XY: 23852 AN XY: 72876

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.334

Alfa AF: 0.132 Hom.: 213

Bravo AF: 0.319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759853; hg19: chr7-134143958; COSMIC: COSV53649543;