rs1869220

Variant names:

• chr10-4837188-C-T
• rs1869220
• NM_001040177.3:c.460-271C>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.460-271C>T 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 152,316 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (149 hom., cov: 33)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.624
• 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=-0.91).
• BP6: Variant 10-4837188-C-T is Benign according to our data. Variant chr10-4837188-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1E2	NM_001040177.3	c.460-271C>T		intron_variant	Intron 4 of 9	ENST00000298375.12	NP_001035267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1E2	ENST00000298375.12	c.460-271C>T		intron_variant	Intron 4 of 9	1	NM_001040177.3	ENSP00000298375.7

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5305 AN: 152198 Hom.: 149 Cov.: 33

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0348 AC: 5302 AN: 152316 Hom.: 149 Cov.: 33 AF XY: 0.0332 AC XY: 2471 AN XY: 74482

African (AFR) AF: 0.00979 AC: 407 AN: 41580

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

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.114 AC: 591 AN: 5172

South Asian (SAS) AF: 0.0217 AC: 105 AN: 4828

European-Finnish (FIN) AF: 0.0154 AC: 163 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0495 AC: 3370 AN: 68022

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0420 Hom.: 21

Bravo AF: 0.0360

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.69
PhyloP100		-0.62
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: rs1869220; hg19: chr10-4879380;