10-4830577-T-C

Position:

• chr10-4830577-T-C

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.40-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,397,112 control chromosomes in the GnomAD database, including 1,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (150 hom., cov: 32)
  • Exomes 𝑓: 0.041 (1324 hom.)
• Consequence: AKR1E2 NM_001040177.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.457

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=-0.83).
• BP6: Variant 10-4830577-T-C is Benign according to our data. Variant chr10-4830577-T-C is described in ClinVar as [Benign]. Clinvar id is 1271836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1E2	NM_001040177.3	c.40-98T>C		intron_variant		ENST00000298375.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1E2	ENST00000298375.12	c.40-98T>C		intron_variant		1	NM_001040177.3	P1

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5308 AN: 152150 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.00987

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: 0.0153

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0495

Gnomad OTH AF: 0.0374

GnomAD4 exome AF: 0.0414 AC: 51495 AN: 1244844 Hom.: 1324 AF XY: 0.0409 AC XY: 25290 AN XY: 618082

Gnomad4 AFR exome AF: 0.00677

Gnomad4 AMR exome AF: 0.0314

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.0167

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0350

GnomAD4 genome AF: 0.0348 AC: 5305 AN: 152268 Hom.: 150 Cov.: 32 AF XY: 0.0332 AC XY: 2471 AN XY: 74450

Gnomad4 AFR AF: 0.00984

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0495

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0419 Hom.: 21

Bravo AF: 0.0361

Asia WGS AF: 0.0540 AC: 187 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 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs3750738; hg19: chr10-4872769; COSMIC: COSV53630082; COSMIC: COSV53630082;