1-45570088-A-T

Variant names:

• chr1-45570088-A-T
• rs3014216
• NM_153326.3:c.*132A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153326.3(AKR1A1):​c.*132A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 917,850 control chromosomes in the GnomAD database, including 107,523 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 0.47 (16877 hom., cov: 32)
  • Exomes 𝑓: 0.49 (90646 hom.)
• Consequence: AKR1A1 NM_153326.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

Genes affected

AKR1A1 (HGNC:380): (aldo-keto reductase family 1 member A1) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member, also known as aldehyde reductase, is involved in the reduction of biogenic and xenobiotic aldehydes and is present in virtually every tissue. Multiple alternatively spliced transcript variants of this gene exist, all encoding the same protein. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1A1	NM_153326.3	c.*132A>T		downstream_gene_variant		ENST00000351829.9	NP_697021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1A1	ENST00000351829.9	c.*132A>T		downstream_gene_variant		1	NM_153326.3	ENSP00000312606.4

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71320 AN: 151932 Hom.: 16892 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.485 AC: 371629 AN: 765800 Hom.: 90646 Cov.: 10 AF XY: 0.485 AC XY: 192535 AN XY: 396888

Gnomad4 AFR exome AF: 0.423 AC: 8298 AN: 19624

Gnomad4 AMR exome AF: 0.558 AC: 19473 AN: 34908

Gnomad4 ASJ exome AF: 0.503 AC: 9241 AN: 18362

Gnomad4 EAS exome AF: 0.649 AC: 22355 AN: 34422

Gnomad4 SAS exome AF: 0.498 AC: 30973 AN: 62230

Gnomad4 FIN exome AF: 0.487 AC: 21419 AN: 44008

Gnomad4 NFE exome AF: 0.469 AC: 240693 AN: 512690

Gnomad4 Remaining exome AF: 0.486 AC: 17844 AN: 36696

GnomAD4 genome AF: 0.469 AC: 71304 AN: 152050 Hom.: 16877 Cov.: 32 AF XY: 0.472 AC XY: 35059 AN XY: 74312

Gnomad4 AFR AF: 0.425 AC: 0.42516 AN: 0.42516

Gnomad4 AMR AF: 0.513 AC: 0.512898 AN: 0.512898

Gnomad4 ASJ AF: 0.507 AC: 0.507493 AN: 0.507493

Gnomad4 EAS AF: 0.624 AC: 0.62355 AN: 0.62355

Gnomad4 SAS AF: 0.506 AC: 0.506022 AN: 0.506022

Gnomad4 FIN AF: 0.483 AC: 0.482971 AN: 0.482971

Gnomad4 NFE AF: 0.468 AC: 0.467637 AN: 0.467637

Gnomad4 OTH AF: 0.456 AC: 0.45584 AN: 0.45584

Alfa AF: 0.312 Hom.: 762

Bravo AF: 0.468

Asia WGS AF: 0.537 AC: 1865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.68
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3014216; hg19: chr1-46035760; COSMIC: COSV61086540;