10-4830364-C-G

Position:

• chr10-4830364-C-G

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.40-311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,170 control chromosomes in the GnomAD database, including 3,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3363 hom., cov: 33)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.471

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=-0.76).
• BP6: Variant 10-4830364-C-G is Benign according to our data. Variant chr10-4830364-C-G is described in ClinVar as [Benign]. Clinvar id is 1239771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3	c.40-311C>G		intron_variant		ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12	c.40-311C>G		intron_variant		1	NM_001040177.3	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31069 AN: 152052 Hom.: 3367 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.204 AC: 31064 AN: 152170 Hom.: 3363 Cov.: 33 AF XY: 0.200 AC XY: 14855 AN XY: 74396

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.232

Alfa AF: 0.200 Hom.: 394

Bravo AF: 0.207

Asia WGS AF: 0.156 AC: 541 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

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.73

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: rs1901644; hg19: chr10-4872556;