13-43578591-C-T

Position:

• chr13-43578591-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347969.2(ENOX1):​c.-219+88888G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,928 control chromosomes in the GnomAD database, including 13,641 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13641 hom., cov: 31)
• Consequence: ENOX1 NM_001347969.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

Genes affected

ENOX1 (HGNC:25474): (ecto-NOX disulfide-thiol exchanger 1) The protein encoded by this gene is involved in plasma membrane electron transport pathways. The encoded protein has both a hydroquinone (NADH) oxidase activity and a protein disulfide-thiol interchange activity. The two activities cycle with a periodicity of 24 minutes, with one activity being at its peak when the other is at its lowest. [provided by RefSeq, Dec 2016]

ENOX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENOX1	NM_001347969.2	c.-219+88888G>A		intron_variant		ENST00000690772.1	NP_001334898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENOX1	ENST00000690772.1	c.-219+88888G>A		intron_variant			NM_001347969.2	ENSP00000509229.1
ENOX1	ENST00000261488.10	c.-219+88851G>A		intron_variant		1		ENSP00000261488.6

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63510 AN: 151810 Hom.: 13629 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.418 AC: 63550 AN: 151928 Hom.: 13641 Cov.: 31 AF XY: 0.425 AC XY: 31586 AN XY: 74250

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.434

Alfa AF: 0.388 Hom.: 15686

Bravo AF: 0.428

Asia WGS AF: 0.559 AC: 1944 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.017
DANN	Benign	0.47

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: rs9533534; hg19: chr13-44152727; COSMIC: COSV54887111;