chr13-43591883-T-C

Variant names:

• chr13-43591883-T-C
• rs17460623
• NM_001347969.2:c.-219+75596A>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+75596A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,024 control chromosomes in the GnomAD database, including 809 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 0.10 (809 hom., cov: 32)
• Consequence: ENOX1 NM_001347969.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	NM_001347969.2	MANE Select	c.-219+75596A>G		intron	N/A	NP_001334898.1
	ENOX1	NM_001347963.2		c.31+75596A>G		intron	N/A	NP_001334892.1
	ENOX1	NM_001127615.3		c.-219+18000A>G		intron	N/A	NP_001121087.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX1	ENST00000690772.1	MANE Select	c.-219+75596A>G		intron	N/A	ENSP00000509229.1
	ENOX1	ENST00000261488.10	TSL:1	c.-219+75559A>G		intron	N/A	ENSP00000261488.6

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15244 AN: 151904 Hom.: 807 Cov.: 32

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0652

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.100 AC: 15260 AN: 152024 Hom.: 809 Cov.: 32 AF XY: 0.0984 AC XY: 7311 AN XY: 74300

African (AFR) AF: 0.0951 AC: 3943 AN: 41452

American (AMR) AF: 0.123 AC: 1877 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0652 AC: 226 AN: 3468

East Asian (EAS) AF: 0.0630 AC: 325 AN: 5160

South Asian (SAS) AF: 0.0316 AC: 152 AN: 4808

European-Finnish (FIN) AF: 0.0948 AC: 1003 AN: 10582

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7400 AN: 67982

Other (OTH) AF: 0.0913 AC: 193 AN: 2114

Alfa AF: 0.105 Hom.: 1170

Bravo AF: 0.104

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.55
PhyloP100		-0.81
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: rs17460623; hg19: chr13-44166019;