7-8488433-T-C

Variant names:

• chr7-8488433-T-C
• rs10486228
• NM_152745.3:c.54+52666T>C

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+52666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,068 control chromosomes in the GnomAD database, including 3,444 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 0.18 (3444 hom., cov: 32)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH1	NM_152745.3	c.54+52666T>C		intron_variant	Intron 2 of 2	ENST00000405863.6	NP_689958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPH1	ENST00000405863.6	c.54+52666T>C		intron_variant	Intron 2 of 2	1	NM_152745.3	ENSP00000384551.1
NXPH1	ENST00000429542.1	c.54+52666T>C		intron_variant	Intron 1 of 1	1		ENSP00000408216.1
NXPH1	ENST00000438764.1	c.54+52666T>C		intron_variant	Intron 2 of 2	4		ENSP00000404689.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27620 AN: 151952 Hom.: 3448 Cov.: 32

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.182 AC: 27621 AN: 152068 Hom.: 3444 Cov.: 32 AF XY: 0.189 AC XY: 14068 AN XY: 74336

African (AFR) AF: 0.0570 AC: 2367 AN: 41528

American (AMR) AF: 0.289 AC: 4411 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3464

East Asian (EAS) AF: 0.612 AC: 3146 AN: 5138

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4826

European-Finnish (FIN) AF: 0.229 AC: 2421 AN: 10578

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12919 AN: 67966

Other (OTH) AF: 0.177 AC: 373 AN: 2106

Alfa AF: 0.185 Hom.: 5696

Bravo AF: 0.184

Asia WGS AF: 0.422 AC: 1464 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-1.3
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: rs10486228; hg19: chr7-8528063; COSMIC: COSV68320122;