chr10-4801186-C-T

Variant names:

• chr10-4801186-C-T
• rs11252748
• ENST00000533295.5:c.-27+14426C>T

Variant summary

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

The ENST00000533295.5(AKR1E2):​c.-27+14426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,054 control chromosomes in the GnomAD database, including 3,973 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 0.20 (3973 hom., cov: 32)
• Consequence: AKR1E2 ENST00000533295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 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+14426C>T		intron_variant	Intron 1 of 5	3		ENSP00000435436.1
AKR1E2	ENST00000462718.7	n.52+14426C>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30694 AN: 151934 Hom.: 3976 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.202 AC: 30702 AN: 152054 Hom.: 3973 Cov.: 32 AF XY: 0.209 AC XY: 15555 AN XY: 74300

African (AFR) AF: 0.0724 AC: 3003 AN: 41506

American (AMR) AF: 0.212 AC: 3243 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3022 AN: 5168

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4818

European-Finnish (FIN) AF: 0.283 AC: 2982 AN: 10532

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15400 AN: 67954

Other (OTH) AF: 0.207 AC: 438 AN: 2116

Alfa AF: 0.228 Hom.: 1582

Bravo AF: 0.192

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.18
DANN	Benign	0.94
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs11252748; hg19: chr10-4843378;