7-8527374-G-T

Variant names:

• chr7-8527374-G-T
• rs1557841
• NM_152745.3:c.54+91607G>T

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+91607G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,098 control chromosomes in the GnomAD database, including 5,135 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 0.23 (5135 hom., cov: 33)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH1	NM_152745.3	c.54+91607G>T		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+91607G>T		intron_variant	Intron 2 of 2	1	NM_152745.3	ENSP00000384551.1
NXPH1	ENST00000429542.1	c.54+91607G>T		intron_variant	Intron 1 of 1	1		ENSP00000408216.1
NXPH1	ENST00000438764.1	c.54+91607G>T		intron_variant	Intron 2 of 2	4		ENSP00000404689.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35155 AN: 151980 Hom.: 5133 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.231 AC: 35158 AN: 152098 Hom.: 5135 Cov.: 33 AF XY: 0.233 AC XY: 17323 AN XY: 74318

African (AFR) AF: 0.0642 AC: 2667 AN: 41522

American (AMR) AF: 0.276 AC: 4216 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3466

East Asian (EAS) AF: 0.154 AC: 792 AN: 5154

South Asian (SAS) AF: 0.185 AC: 894 AN: 4824

European-Finnish (FIN) AF: 0.370 AC: 3900 AN: 10540

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.305 AC: 20766 AN: 67992

Other (OTH) AF: 0.224 AC: 473 AN: 2114

Alfa AF: 0.257 Hom.: 2928

Bravo AF: 0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		0.62
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: rs1557841; hg19: chr7-8567004;