chr10-4833070-A-G

Variant names:

• chr10-4833070-A-G
• rs2167703
• NM_001040177.3:c.208-280A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.99).
• BP6: Variant 10-4833070-A-G is Benign according to our data. Variant chr10-4833070-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040177.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	NM_001040177.3	MANE Select	c.208-280A>G		intron	N/A	NP_001035267.1
	AKR1E2	NM_001271021.2		c.208-280A>G		intron	N/A	NP_001257950.1
	AKR1E2	NM_001271025.2		c.208-280A>G		intron	N/A	NP_001257954.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	ENST00000298375.12	TSL:1 MANE Select	c.208-280A>G		intron	N/A	ENSP00000298375.7
	AKR1E2	ENST00000334019.4	TSL:1	c.208-280A>G		intron	N/A	ENSP00000335034.4
	AKR1E2	ENST00000532248.5	TSL:1	c.208-280A>G		intron	N/A	ENSP00000432947.1

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

African (AFR) AF: 0.181 AC: 7528 AN: 41516

American (AMR) AF: 0.194 AC: 2958 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3472

East Asian (EAS) AF: 0.110 AC: 571 AN: 5188

South Asian (SAS) AF: 0.198 AC: 955 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1681 AN: 10602

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15642 AN: 67998

Other (OTH) AF: 0.232 AC: 491 AN: 2112

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

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.30
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2167703; hg19: chr10-4875262;