7-8520661-C-T

Variant names:

• chr7-8520661-C-T
• rs10255873
• NM_152745.3:c.54+84894C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000405863.6(NXPH1):​c.54+84894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,904 control chromosomes in the GnomAD database, including 9,040 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 0.34 (9040 hom., cov: 32)
• Consequence: NXPH1 ENST00000405863.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405863.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPH1	NM_152745.3	MANE Select	c.54+84894C>T		intron	N/A	NP_689958.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPH1	ENST00000405863.6	TSL:1 MANE Select	c.54+84894C>T		intron	N/A	ENSP00000384551.1
	NXPH1	ENST00000429542.1	TSL:1	c.54+84894C>T		intron	N/A	ENSP00000408216.1
	NXPH1	ENST00000438764.1	TSL:4	c.54+84894C>T		intron	N/A	ENSP00000404689.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51541 AN: 151786 Hom.: 9022 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.340 AC: 51606 AN: 151904 Hom.: 9040 Cov.: 32 AF XY: 0.342 AC XY: 25366 AN XY: 74186

African (AFR) AF: 0.383 AC: 15877 AN: 41416

American (AMR) AF: 0.315 AC: 4810 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1957 AN: 5134

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4822

European-Finnish (FIN) AF: 0.410 AC: 4321 AN: 10544

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21028 AN: 67932

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.305 Hom.: 12267

Bravo AF: 0.335

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.55
PhyloP100		0.96
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: rs10255873; hg19: chr7-8560291;