chr10-4826111-T-A

Position:

• chr10-4826111-T-A

Variant summary

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

The ENST00000533295.5(AKR1E2):​c.51+1073T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 404,366 control chromosomes in the GnomAD database, including 1,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (644 hom., cov: 34)
  • Exomes 𝑓: 0.083 (991 hom.)
• Consequence: AKR1E2 ENST00000533295.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.65

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=-0.58).
• BP6: Variant 10-4826111-T-A is Benign according to our data. Variant chr10-4826111-T-A is described in ClinVar as [Benign]. Clinvar id is 1229889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	XM_011519715.3	c.51+1073T>A		intron_variant
AKR1E2	XR_001747220.2	n.66+1073T>A		intron_variant, non_coding_transcript_variant
AKR1E2	XR_930518.3	n.66+1073T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000533295.5	c.51+1073T>A		intron_variant		3
AKR1E2	ENST00000462718.7	n.53-4564T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13295 AN: 152144 Hom.: 645 Cov.: 34

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.0832

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.0829 AC: 20898 AN: 252106 Hom.: 991 AF XY: 0.0827 AC XY: 10590 AN XY: 127996

Gnomad4 AFR exome AF: 0.0962

Gnomad4 AMR exome AF: 0.0642

Gnomad4 ASJ exome AF: 0.0783

Gnomad4 EAS exome AF: 0.000398

Gnomad4 SAS exome AF: 0.0607

Gnomad4 FIN exome AF: 0.0933

Gnomad4 NFE exome AF: 0.0937

Gnomad4 OTH exome AF: 0.0824

GnomAD4 genome AF: 0.0874 AC: 13301 AN: 152260 Hom.: 644 Cov.: 34 AF XY: 0.0862 AC XY: 6418 AN XY: 74456

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.0661

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.0832

Gnomad4 NFE AF: 0.0936

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.101 Hom.: 88

Bravo AF: 0.0852

Asia WGS AF: 0.0390 AC: 137 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.8
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11252766; hg19: chr10-4868303;