chr7-8463913-T-C

Position:

• chr7-8463913-T-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+28146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,072 control chromosomes in the GnomAD database, including 29,497 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 0.59 (29497 hom., cov: 32)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPH1	NM_152745.3	c.54+28146T>C		intron_variant		ENST00000405863.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPH1	ENST00000405863.6	c.54+28146T>C		intron_variant		1	NM_152745.3	P1
NXPH1	ENST00000429542.1	c.54+28146T>C		intron_variant		1
NXPH1	ENST00000438764.1	c.54+28146T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90254 AN: 151954 Hom.: 29459 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.594 AC: 90349 AN: 152072 Hom.: 29497 Cov.: 32 AF XY: 0.595 AC XY: 44248 AN XY: 74334

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.560

Alfa AF: 0.478 Hom.: 36174

Bravo AF: 0.612

Asia WGS AF: 0.755 AC: 2622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.073
DANN	Benign	0.56

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: rs2040891; hg19: chr7-8503543;