rs75079745

Variant names:

• chr10-4826678-T-C
• rs75079745
• NM_001040177.3:c.39+315T>C

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.39+315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,194 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.033 (131 hom., cov: 32)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.405
• 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=-0.82).
• BP6: Variant 10-4826678-T-C is Benign according to our data. Variant chr10-4826678-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1316791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 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.39+315T>C		intron	N/A	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.39+315T>C		intron	N/A	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.39+315T>C		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.39+315T>C		intron	N/A	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.39+315T>C		intron	N/A	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.39+315T>C		intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4977 AN: 152076 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.00949

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0327 AC: 4974 AN: 152194 Hom.: 131 Cov.: 32 AF XY: 0.0311 AC XY: 2314 AN XY: 74410

African (AFR) AF: 0.00946 AC: 393 AN: 41552

American (AMR) AF: 0.0345 AC: 528 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.112 AC: 573 AN: 5124

South Asian (SAS) AF: 0.0215 AC: 104 AN: 4828

European-Finnish (FIN) AF: 0.0141 AC: 149 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0455 AC: 3095 AN: 67998

Other (OTH) AF: 0.0369 AC: 78 AN: 2116

Alfa AF: 0.0362 Hom.: 17

Bravo AF: 0.0345

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.38
PhyloP100		-0.41
PromoterAI		-0.061	Neutral
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: rs75079745; hg19: chr10-4868870;