NM_001040177.3:c.103G>A

Variant names:

• chr10-4830738-G-A
• rs61745201
• NM_001040177.3:c.103G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040177.3(AKR1E2):​c.103G>A​(p.Asp35Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,613,988 control chromosomes in the GnomAD database, including 3,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (262 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3332 hom.)
• Consequence: AKR1E2 NM_001040177.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.41
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004357338).
• BP6: Variant 10-4830738-G-A is Benign according to our data. Variant chr10-4830738-G-A is described in ClinVar as Benign. ClinVar VariationId is 677203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0671 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	NM_001040177.3	MANE Select	c.103G>A	p.Asp35Asn	missense	Exon 2 of 10	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.103G>A	p.Asp35Asn	missense	Exon 2 of 8	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.103G>A	p.Asp35Asn	missense	Exon 2 of 7	NP_001257954.1	Q96JD6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1E2	ENST00000298375.12	TSL:1 MANE Select	c.103G>A	p.Asp35Asn	missense	Exon 2 of 10	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.103G>A	p.Asp35Asn	missense	Exon 2 of 8	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.103G>A	p.Asp35Asn	missense	Exon 2 of 7	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7896 AN: 152058 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0450

GnomAD2 exomes AF: 0.0518 AC: 13035 AN: 251466 AF XY: 0.0514

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.0391

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0888

Gnomad NFE exome AF: 0.0715

Gnomad OTH exome AF: 0.0526

GnomAD4 exome AF: 0.0641 AC: 93653 AN: 1461812 Hom.: 3332 Cov.: 31 AF XY: 0.0629 AC XY: 45751 AN XY: 727206

African (AFR) AF: 0.0372 AC: 1247 AN: 33478

American (AMR) AF: 0.0266 AC: 1191 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 1028 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0265 AC: 2289 AN: 86236

European-Finnish (FIN) AF: 0.0895 AC: 4781 AN: 53416

Middle Eastern (MID) AF: 0.0302 AC: 174 AN: 5768

European-Non Finnish (NFE) AF: 0.0715 AC: 79512 AN: 1111966

Other (OTH) AF: 0.0568 AC: 3430 AN: 60392

GnomAD4 genome AF: 0.0519 AC: 7900 AN: 152176 Hom.: 262 Cov.: 32 AF XY: 0.0508 AC XY: 3781 AN XY: 74400

African (AFR) AF: 0.0333 AC: 1384 AN: 41530

American (AMR) AF: 0.0309 AC: 472 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4818

European-Finnish (FIN) AF: 0.0815 AC: 862 AN: 10582

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4677 AN: 68006

Other (OTH) AF: 0.0445 AC: 94 AN: 2110

Alfa AF: 0.0611 Hom.: 607

Bravo AF: 0.0488

TwinsUK AF: 0.0696 AC: 258

ALSPAC AF: 0.0623 AC: 240

ESP6500AA AF: 0.0354 AC: 156

ESP6500EA AF: 0.0658 AC: 566

ExAC AF: 0.0544 AC: 6604

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0609

EpiControl AF: 0.0655

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0044	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	4.1	H
PhyloP100		7.4
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.090	B
Vest4		0.25
MPC		0.16
ClinPred		0.10	T
GERP RS		3.0
Varity_R		0.62
gMVP		0.92
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61745201; hg19: chr10-4872930; COSMIC: COSV107320772; COSMIC: COSV107320772;