rs1901644

Variant names:

• chr10-4830364-C-G
• rs1901644
• NM_001040177.3:c.40-311C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-4830364-C-G
• chr10-4830364-C-T

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.40-311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,170 control chromosomes in the GnomAD database, including 3,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3363 hom., cov: 33)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.471
• Publications: 4 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=-0.76).
• BP6: Variant 10-4830364-C-G is Benign according to our data. Variant chr10-4830364-C-G is described in ClinVar as Benign. ClinVar VariationId is 1239771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 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.40-311C>G		intron	N/A	NP_001035267.1	Q96JD6-1
	AKR1E2	NM_001271021.2		c.40-311C>G		intron	N/A	NP_001257950.1	Q96JD6-2
	AKR1E2	NM_001271025.2		c.40-311C>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.40-311C>G		intron	N/A	ENSP00000298375.7	Q96JD6-1
	AKR1E2	ENST00000334019.4	TSL:1	c.40-311C>G		intron	N/A	ENSP00000335034.4	Q96JD6-2
	AKR1E2	ENST00000532248.5	TSL:1	c.40-311C>G		intron	N/A	ENSP00000432947.1	Q96JD6-3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31069 AN: 152052 Hom.: 3367 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.204 AC: 31064 AN: 152170 Hom.: 3363 Cov.: 33 AF XY: 0.200 AC XY: 14855 AN XY: 74396

African (AFR) AF: 0.181 AC: 7507 AN: 41502

American (AMR) AF: 0.193 AC: 2946 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3470

East Asian (EAS) AF: 0.109 AC: 565 AN: 5174

South Asian (SAS) AF: 0.198 AC: 954 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1675 AN: 10588

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15491 AN: 68006

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.200 Hom.: 394

Bravo AF: 0.207

Asia WGS AF: 0.156 AC: 541 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.76
CADD	Benign	1.3
DANN	Benign	0.73
PhyloP100		-0.47
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: rs1901644; hg19: chr10-4872556;