chr7-8438782-A-C

Position:

• chr7-8438782-A-C

Variant summary

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

The NM_152745.3(NXPH1):​c.54+3015A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,120 control chromosomes in the GnomAD database, including 38,760 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 0.69 (38760 hom., cov: 33)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

Genes affected

NXPH1 (HGNC:20693): (neurexophilin 1) This gene is a member of the neurexophilin family and encodes a secreted protein with a variable N-terminal domain, a highly conserved, N-glycosylated central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein forms a very tight complex with alpha neurexins, a group of proteins that promote adhesion between dendrites and axons. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPH1	NM_152745.3	c.54+3015A>C		intron_variant		ENST00000405863.6	NP_689958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXPH1	ENST00000405863.6	c.54+3015A>C		intron_variant		1	NM_152745.3	ENSP00000384551	P1
NXPH1	ENST00000429542.1	c.54+3015A>C		intron_variant		1		ENSP00000408216
NXPH1	ENST00000438764.1	c.54+3015A>C		intron_variant		4		ENSP00000404689

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105410 AN: 152002 Hom.: 38752 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.693 AC: 105445 AN: 152120 Hom.: 38760 Cov.: 33 AF XY: 0.696 AC XY: 51737 AN XY: 74362

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.713

Alfa AF: 0.777 Hom.: 23557

Bravo AF: 0.672

Asia WGS AF: 0.858 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.8
DANN	Benign	0.66

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: rs10247446; hg19: chr7-8478412;