10-4826082-G-C

Position:

• chr10-4826082-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000533295.5(AKR1E2):​c.51+1044G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 393,256 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (9 hom., cov: 34)
  • Exomes 𝑓: 0.0079 (13 hom.)
• Consequence: AKR1E2 ENST00000533295.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.957

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-4826082-G-C is Benign according to our data. Variant chr10-4826082-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	XM_011519715.3	c.51+1044G>C		intron_variant
AKR1E2	XR_001747220.2	n.66+1044G>C		intron_variant, non_coding_transcript_variant
AKR1E2	XR_930518.3	n.66+1044G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000533295.5	c.51+1044G>C		intron_variant		3
AKR1E2	ENST00000462718.7	n.53-4593G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 892 AN: 152218 Hom.: 9 Cov.: 34

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00908

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.00792 AC: 1908 AN: 240922 Hom.: 13 AF XY: 0.00810 AC XY: 992 AN XY: 122458

Gnomad4 AFR exome AF: 0.00132

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00224

Gnomad4 EAS exome AF: 0.0000445

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.00819

Gnomad4 NFE exome AF: 0.00979

Gnomad4 OTH exome AF: 0.00718

GnomAD4 genome AF: 0.00585 AC: 891 AN: 152334 Hom.: 9 Cov.: 34 AF XY: 0.00602 AC XY: 448 AN XY: 74480

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.00908

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00948 Hom.: 1

Bravo AF: 0.00484

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.6
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs143761184; hg19: chr10-4868274;