10-4802973-T-C

Variant names:

• chr10-4802973-T-C
• rs2961599
• ENST00000533295.5:c.-27+16213T>C

Variant summary

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

The ENST00000533295.5(AKR1E2):​c.-27+16213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,050 control chromosomes in the GnomAD database, including 31,576 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 0.64 (31576 hom., cov: 32)
• Consequence: AKR1E2 ENST00000533295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 1 publications found

Genes affected

AKR1E2 (HGNC:23437): (aldo-keto reductase family 1 member E2) The protein encoded by this gene is a member of the aldo-keto reductase superfamily. Members in this family are characterized by their structure (evolutionarily highly conserved TIM barrel) and function (NAD(P)H-dependent oxido-reduction of carbonyl groups). Transcripts of this gene have been reported in specimens of human testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

AKR1E2 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1E2	ENST00000533295.5	c.-27+16213T>C		intron_variant	Intron 1 of 5	3		ENSP00000435436.1
AKR1E2	ENST00000462718.7	n.52+16213T>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96522 AN: 151932 Hom.: 31555 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.635 AC: 96584 AN: 152050 Hom.: 31576 Cov.: 32 AF XY: 0.643 AC XY: 47797 AN XY: 74326

African (AFR) AF: 0.480 AC: 19880 AN: 41428

American (AMR) AF: 0.723 AC: 11061 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2124 AN: 3468

East Asian (EAS) AF: 0.915 AC: 4735 AN: 5174

South Asian (SAS) AF: 0.688 AC: 3311 AN: 4812

European-Finnish (FIN) AF: 0.750 AC: 7920 AN: 10566

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45483 AN: 67996

Other (OTH) AF: 0.636 AC: 1343 AN: 2112

Alfa AF: 0.655 Hom.: 19916

Bravo AF: 0.629

Asia WGS AF: 0.772 AC: 2684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.5
DANN	Benign	0.53
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs2961599; hg19: chr10-4845165;