7-8627460-A-G

Variant names:

• chr7-8627460-A-G
• rs4455737
• NM_152745.3:c.55-123548A>G

Variant summary

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

The NM_152745.3(NXPH1):​c.55-123548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,026 control chromosomes in the GnomAD database, including 12,263 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 0.38 (12263 hom., cov: 32)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 1 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]

LOC105375144 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH1	NM_152745.3	c.55-123548A>G		intron_variant	Intron 2 of 2	ENST00000405863.6	NP_689958.1
LOC105375144	XR_007060208.1	n.79+4925T>C		intron_variant	Intron 1 of 3
LOC105375144	XR_001745084.2	n.-152T>C		upstream_gene_variant
LOC105375144	XR_927017.4	n.-152T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPH1	ENST00000405863.6	c.55-123548A>G		intron_variant	Intron 2 of 2	1	NM_152745.3	ENSP00000384551.1
NXPH1	ENST00000429542.1	c.55-123548A>G		intron_variant	Intron 1 of 1	1		ENSP00000408216.1
NXPH1	ENST00000438764.1	c.55-123548A>G		intron_variant	Intron 2 of 2	4		ENSP00000404689.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58158 AN: 151908 Hom.: 12229 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.383 AC: 58225 AN: 152026 Hom.: 12263 Cov.: 32 AF XY: 0.380 AC XY: 28243 AN XY: 74314

African (AFR) AF: 0.568 AC: 23541 AN: 41464

American (AMR) AF: 0.317 AC: 4832 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3466

East Asian (EAS) AF: 0.176 AC: 908 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4822

European-Finnish (FIN) AF: 0.369 AC: 3911 AN: 10588

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21656 AN: 67942

Other (OTH) AF: 0.337 AC: 711 AN: 2108

Alfa AF: 0.289 Hom.: 1290

Bravo AF: 0.388

Asia WGS AF: 0.267 AC: 928 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.75
PhyloP100		-0.084
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: rs4455737; hg19: chr7-8667090;