7-8500665-A-G

Variant names:

• chr7-8500665-A-G
• rs757705
• NM_152745.3:c.54+64898A>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.54+64898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,992 control chromosomes in the GnomAD database, including 25,901 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 0.57 (25901 hom., cov: 33)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720
• Publications: 5 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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152745.3. 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
	NXPH1	NM_152745.3	MANE Select	c.54+64898A>G		intron	N/A	NP_689958.1	P58417

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPH1	ENST00000405863.6	TSL:1 MANE Select	c.54+64898A>G		intron	N/A	ENSP00000384551.1	P58417
	NXPH1	ENST00000429542.1	TSL:1	c.54+64898A>G		intron	N/A	ENSP00000408216.1	C9JPD0
	NXPH1	ENST00000438764.1	TSL:4	c.54+64898A>G		intron	N/A	ENSP00000404689.1	C9JE46

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87069 AN: 151874 Hom.: 25890 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.573 AC: 87110 AN: 151992 Hom.: 25901 Cov.: 33 AF XY: 0.584 AC XY: 43397 AN XY: 74284

African (AFR) AF: 0.685 AC: 28397 AN: 41478

American (AMR) AF: 0.598 AC: 9128 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3468

East Asian (EAS) AF: 0.905 AC: 4654 AN: 5144

South Asian (SAS) AF: 0.579 AC: 2793 AN: 4822

European-Finnish (FIN) AF: 0.598 AC: 6315 AN: 10566

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32043 AN: 67940

Other (OTH) AF: 0.554 AC: 1172 AN: 2114

Alfa AF: 0.508 Hom.: 42699

Bravo AF: 0.580

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.72
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: rs757705; hg19: chr7-8540295;