10-4826678-T-C

Position:

• chr10-4826678-T-C

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.39+315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,194 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.033 (131 hom., cov: 32)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.405

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 10-4826678-T-C is Benign according to our data. Variant chr10-4826678-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3	c.39+315T>C		intron_variant		ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12	c.39+315T>C		intron_variant		1	NM_001040177.3	P1

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4977 AN: 152076 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.00949

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0327 AC: 4974 AN: 152194 Hom.: 131 Cov.: 32 AF XY: 0.0311 AC XY: 2314 AN XY: 74410

Gnomad4 AFR AF: 0.00946

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0362 Hom.: 17

Bravo AF: 0.0345

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.38

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: rs75079745; hg19: chr10-4868870;