chr10-4830495-T-G

Variant names:

• chr10-4830495-T-G
• rs3750737
• NM_001040177.3:c.40-180T>G

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.40-180T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 152,296 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.035 (150 hom., cov: 32)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74
• Publications: 0 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 (BayesDel_noAF=-0.85).
• BP6: Variant 10-4830495-T-G is Benign according to our data. Variant chr10-4830495-T-G is described in ClinVar as Benign. ClinVar VariationId is 1279953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 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.40-180T>G		intron	N/A	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.40-180T>G		intron	N/A	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.40-180T>G		intron	N/A	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.40-180T>G		intron	N/A	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.40-180T>G		intron	N/A	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.40-180T>G		intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5310 AN: 152178 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.00984

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0374

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

GnomAD4 genome AF: 0.0348 AC: 5307 AN: 152296 Hom.: 150 Cov.: 32 AF XY: 0.0332 AC XY: 2470 AN XY: 74462

African (AFR) AF: 0.00981 AC: 408 AN: 41576

American (AMR) AF: 0.0348 AC: 532 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.115 AC: 595 AN: 5180

South Asian (SAS) AF: 0.0216 AC: 104 AN: 4824

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0495 AC: 3370 AN: 68016

Other (OTH) AF: 0.0375 AC: 79 AN: 2108

Alfa AF: 0.0423 Hom.: 21

Bravo AF: 0.0361

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.084
DANN	Benign	0.67
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs3750737; hg19: chr10-4872687;