chr13-43642928-T-C

Variant names:

• chr13-43642928-T-C
• rs4942242
• NM_001347969.2:c.-219+24551A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347969.2(ENOX1):​c.-219+24551A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,984 control chromosomes in the GnomAD database, including 21,181 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 0.53 (21181 hom., cov: 32)
• Consequence: ENOX1 NM_001347969.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347969.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	NM_001347969.2	MANE Select	c.-219+24551A>G		intron	N/A	NP_001334898.1	A0A024RDT8
	ENOX1	NM_001347963.2		c.31+24551A>G		intron	N/A	NP_001334892.1
	ENOX1	NM_001242863.3		c.-219+24540A>G		intron	N/A	NP_001229792.1	Q8TC92-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	ENST00000690772.1	MANE Select	c.-219+24551A>G		intron	N/A	ENSP00000509229.1	Q8TC92-1
	ENOX1	ENST00000261488.10	TSL:1	c.-219+24514A>G		intron	N/A	ENSP00000261488.6	Q8TC92-1
	ENOX1	ENST00000871211.1		c.-271+24551A>G		intron	N/A	ENSP00000541270.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79841 AN: 151866 Hom.: 21153 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.526 AC: 79909 AN: 151984 Hom.: 21181 Cov.: 32 AF XY: 0.527 AC XY: 39112 AN XY: 74278

African (AFR) AF: 0.471 AC: 19515 AN: 41452

American (AMR) AF: 0.489 AC: 7471 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2043 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2883 AN: 5172

South Asian (SAS) AF: 0.594 AC: 2858 AN: 4814

European-Finnish (FIN) AF: 0.607 AC: 6415 AN: 10560

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36959 AN: 67918

Other (OTH) AF: 0.523 AC: 1106 AN: 2116

Alfa AF: 0.536 Hom.: 40729

Bravo AF: 0.513

Asia WGS AF: 0.560 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.7
DANN	Benign	0.78
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4942242; hg19: chr13-44217064; COSMIC: COSV54916080;