rs2167703

Positions:

• chr10-4833070-A-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.208-280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,202 control chromosomes in the GnomAD database, including 3,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3398 hom., cov: 33)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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=-0.99).
• BP6: Variant 10-4833070-A-G is Benign according to our data. Variant chr10-4833070-A-G is described in ClinVar as [Benign]. Clinvar id is 1241312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3	c.208-280A>G		intron_variant		ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12	c.208-280A>G		intron_variant		1	NM_001040177.3	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31266 AN: 152084 Hom.: 3402 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.205 AC: 31261 AN: 152202 Hom.: 3398 Cov.: 33 AF XY: 0.201 AC XY: 14953 AN XY: 74428

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.232

Alfa AF: 0.210 Hom.: 421

Bravo AF: 0.208

Asia WGS AF: 0.156 AC: 542 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	-0.99
CADD	Benign	1.3
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2167703; hg19: chr10-4875262;