chr7-8744114-T-C

Position:

• chr7-8744114-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.55-6894T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,296 control chromosomes in the GnomAD database, including 260 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 0.036 (260 hom., cov: 32)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPH1	NM_152745.3	c.55-6894T>C		intron_variant		ENST00000405863.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPH1	ENST00000405863.6	c.55-6894T>C		intron_variant		1	NM_152745.3	P1
NXPH1	ENST00000429542.1	c.55-6894T>C		intron_variant		1
NXPH1	ENST00000438764.1	c.55-6894T>C		intron_variant		4
NXPH1	ENST00000497400.1	n.60-6894T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5559 AN: 152178 Hom.: 260 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0365 AC: 5557 AN: 152296 Hom.: 260 Cov.: 32 AF XY: 0.0408 AC XY: 3038 AN XY: 74474

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.0736

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0203 Hom.: 10

Bravo AF: 0.0414

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
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: rs10486251; hg19: chr7-8783744;