10-4825928-T-G

Variant names:

• chr10-4825928-T-G
• rs2961565
• ENST00000533295.5:c.51+890T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000533295.5(AKR1E2):​c.51+890T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 151,466 control chromosomes in the GnomAD database, including 55,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (55454 hom., cov: 33)
• Consequence: AKR1E2 ENST00000533295.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 10-4825928-T-G is Benign according to our data. Variant chr10-4825928-T-G is described in ClinVar as Benign. ClinVar VariationId is 1239488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533295.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	NR_073126.1		n.-249T>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	ENST00000533295.5	TSL:3	c.51+890T>G		intron	N/A	ENSP00000435436.1	E9PK93
	AKR1E2	ENST00000462718.7	TSL:5	n.53-4747T>G		intron	N/A
	AKR1E2	ENST00000474119.5	TSL:2	n.-623T>G		upstream_gene	N/A	ENSP00000434437.1	G3V1C1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 128915 AN: 151352 Hom.: 55429 Cov.: 33

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.852 AC: 128991 AN: 151466 Hom.: 55454 Cov.: 33 AF XY: 0.854 AC XY: 63297 AN XY: 74084

African (AFR) AF: 0.699 AC: 28529 AN: 40792

American (AMR) AF: 0.909 AC: 13902 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3206 AN: 3472

East Asian (EAS) AF: 0.981 AC: 5064 AN: 5162

South Asian (SAS) AF: 0.853 AC: 4109 AN: 4818

European-Finnish (FIN) AF: 0.922 AC: 9777 AN: 10606

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.904 AC: 61488 AN: 68022

Other (OTH) AF: 0.874 AC: 1837 AN: 2102

Alfa AF: 0.860 Hom.: 2340

Bravo AF: 0.845

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.090
PhyloP100		-2.3
PromoterAI		0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2961565; hg19: chr10-4868120;