rs147492521

Variant names:

• chrX-130656575-C-T
• rs147492521
• NM_006375.4:c.1129+6G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-130656575-C-T
• chrX-130656575-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006375.4(ENOX2):​c.1129+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,032,789 control chromosomes in the GnomAD database, including 72 homozygotes. There are 3,574 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (4 hom., 249 hem., cov: 24)
  • Exomes 𝑓: 0.013 (68 hom. 3325 hem.)
• Consequence: ENOX2 NM_006375.4 splice_region, intron
• Scores: Splicing: ADA: 0.0004812
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.439
• Publications: 1 publications found

Genes affected

ENOX2 (HGNC:2259): (ecto-NOX disulfide-thiol exchanger 2) This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-130656575-C-T is Benign according to our data. Variant chrX-130656575-C-T is described in ClinVar as Benign. ClinVar VariationId is 789254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0129 (11875/920381) while in subpopulation NFE AF = 0.0159 (10899/685912). AF 95% confidence interval is 0.0156. There are 68 homozygotes in GnomAdExome4. There are 3325 alleles in the male GnomAdExome4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006375.4. 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
	ENOX2	NM_006375.4	MANE Select	c.1129+6G>A		splice_region intron	N/A	NP_006366.2
	ENOX2	NM_001382518.1		c.1405+6G>A		splice_region intron	N/A	NP_001369447.1	A0A8I5KRI1
	ENOX2	NM_001382516.1		c.1216+6G>A		splice_region intron	N/A	NP_001369445.1	Q16206-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENOX2	ENST00000394363.6	TSL:2 MANE Select	c.1129+6G>A		splice_region intron	N/A	ENSP00000377890.1	Q16206-2
	ENOX2	ENST00000370927.5	TSL:1	c.1216+6G>A		splice_region intron	N/A	ENSP00000359965.1	Q16206-1
	ENOX2	ENST00000686943.1		c.1405+6G>A		splice_region intron	N/A	ENSP00000509235.1	A0A8I5KRI1

Frequencies

GnomAD3 genomes AF: 0.00874 AC: 982 AN: 112356 Hom.: 4 Cov.: 24

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00816

Gnomad ASJ AF: 0.00414

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.00262

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.00933

GnomAD2 exomes AF: 0.00840 AC: 1427 AN: 169902 AF XY: 0.00855

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00615

Gnomad ASJ exome AF: 0.00512

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00350

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.00745

GnomAD4 exome AF: 0.0129 AC: 11875 AN: 920381 Hom.: 68 Cov.: 16 AF XY: 0.0125 AC XY: 3325 AN XY: 265109

African (AFR) AF: 0.00159 AC: 36 AN: 22674

American (AMR) AF: 0.00568 AC: 185 AN: 32572

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 119 AN: 17923

East Asian (EAS) AF: 0.00 AC: 0 AN: 29241

South Asian (SAS) AF: 0.00269 AC: 129 AN: 48037

European-Finnish (FIN) AF: 0.00307 AC: 124 AN: 40340

Middle Eastern (MID) AF: 0.00406 AC: 15 AN: 3691

European-Non Finnish (NFE) AF: 0.0159 AC: 10899 AN: 685912

Other (OTH) AF: 0.00920 AC: 368 AN: 39991

GnomAD4 genome AF: 0.00872 AC: 980 AN: 112408 Hom.: 4 Cov.: 24 AF XY: 0.00720 AC XY: 249 AN XY: 34582

African (AFR) AF: 0.00190 AC: 59 AN: 30988

American (AMR) AF: 0.00815 AC: 87 AN: 10674

Ashkenazi Jewish (ASJ) AF: 0.00414 AC: 11 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3590

South Asian (SAS) AF: 0.00112 AC: 3 AN: 2680

European-Finnish (FIN) AF: 0.00262 AC: 16 AN: 6102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0148 AC: 787 AN: 53297

Other (OTH) AF: 0.00921 AC: 14 AN: 1520

Alfa AF: 0.0105 Hom.: 80

Bravo AF: 0.00800

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		-0.44
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00048
dbscSNV1_RF	Benign	0.084
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: rs147492521; hg19: chrX-129790549;