10-4830425-C-T

Position:

• chr10-4830425-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040177.3(AKR1E2):​c.40-250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,138 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (309 hom., cov: 32)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.928

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-4830425-C-T is Benign according to our data. Variant chr10-4830425-C-T is described in ClinVar as [Benign]. Clinvar id is 1258361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3	c.40-250C>T		intron_variant		ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12	c.40-250C>T		intron_variant		1	NM_001040177.3	P1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8923 AN: 152022 Hom.: 309 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0239

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0587 AC: 8929 AN: 152138 Hom.: 309 Cov.: 32 AF XY: 0.0573 AC XY: 4263 AN XY: 74372

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0239

Gnomad4 FIN AF: 0.0818

Gnomad4 NFE AF: 0.0689

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0644 Hom.: 76

Bravo AF: 0.0565

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs56039972; hg19: chr10-4872617;