chr10-4826253-G-T

Position:

• chr10-4826253-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040177.3(AKR1E2):​c.-72G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,187,338 control chromosomes in the GnomAD database, including 426,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (48125 hom., cov: 35)
  • Exomes 𝑓: 0.85 (378374 hom.)
• Consequence: AKR1E2 NM_001040177.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.127

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 10-4826253-G-T is Benign according to our data. Variant chr10-4826253-G-T is described in ClinVar as [Benign]. Clinvar id is 1238227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3	c.-72G>T		5_prime_UTR_variant	1/10	ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12	c.-72G>T		5_prime_UTR_variant	1/10	1	NM_001040177.3	P1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119162 AN: 152040 Hom.: 48101 Cov.: 35

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.854 AC: 883669 AN: 1035188 Hom.: 378374 Cov.: 18 AF XY: 0.854 AC XY: 418448 AN XY: 489866

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.887

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 0.872

Gnomad4 SAS exome AF: 0.843

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.858

Gnomad4 OTH exome AF: 0.851

GnomAD4 genome AF: 0.784 AC: 119224 AN: 152150 Hom.: 48125 Cov.: 35 AF XY: 0.790 AC XY: 58752 AN XY: 74390

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.914

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.816

Alfa AF: 0.804 Hom.: 8649

Bravo AF: 0.774

Asia WGS AF: 0.834 AC: 2896 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.4
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2924275; hg19: chr10-4868445;