chr7-8438782-A-C

Variant names:

• chr7-8438782-A-C
• rs10247446
• NM_152745.3:c.54+3015A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NXPH1	NM_152745.3	c.54+3015A>C		intron_variant	Intron 2 of 2	ENST00000405863.6	NP_689958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPH1	ENST00000405863.6	c.54+3015A>C		intron_variant	Intron 2 of 2	1	NM_152745.3	ENSP00000384551.1
NXPH1	ENST00000429542.1	c.54+3015A>C		intron_variant	Intron 1 of 1	1		ENSP00000408216.1
NXPH1	ENST00000438764.1	c.54+3015A>C		intron_variant	Intron 2 of 2	4		ENSP00000404689.1

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

African (AFR) AF: 0.429 AC: 17777 AN: 41454

American (AMR) AF: 0.675 AC: 10317 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3468

East Asian (EAS) AF: 0.906 AC: 4698 AN: 5186

South Asian (SAS) AF: 0.826 AC: 3988 AN: 4826

European-Finnish (FIN) AF: 0.792 AC: 8376 AN: 10572

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54910 AN: 68004

Other (OTH) AF: 0.713 AC: 1505 AN: 2112

Alfa AF: 0.775 Hom.: 26094

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
PhyloP100		0.21
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: rs10247446; hg19: chr7-8478412;