rs2214512

Variant names:

• chr7-8547055-G-A
• rs2214512
• NM_152745.3:c.54+111288G>A

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+111288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 151,368 control chromosomes in the GnomAD database, including 621 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 0.085 (621 hom., cov: 32)
• Consequence: NXPH1 NM_152745.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH1	NM_152745.3	c.54+111288G>A		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+111288G>A		intron_variant	Intron 2 of 2	1	NM_152745.3	ENSP00000384551.1
NXPH1	ENST00000429542.1	c.54+111288G>A		intron_variant	Intron 1 of 1	1		ENSP00000408216.1
NXPH1	ENST00000438764.1	c.54+111288G>A		intron_variant	Intron 2 of 2	4		ENSP00000404689.1

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12924 AN: 151250 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000782

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.0910

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

GnomAD4 genome AF: 0.0855 AC: 12940 AN: 151368 Hom.: 621 Cov.: 32 AF XY: 0.0828 AC XY: 6123 AN XY: 73948

African (AFR) AF: 0.115 AC: 4745 AN: 41374

American (AMR) AF: 0.0617 AC: 936 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 346 AN: 3454

East Asian (EAS) AF: 0.000784 AC: 4 AN: 5102

South Asian (SAS) AF: 0.0672 AC: 324 AN: 4818

European-Finnish (FIN) AF: 0.0378 AC: 401 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0864 AC: 5836 AN: 67556

Other (OTH) AF: 0.0895 AC: 188 AN: 2100

Alfa AF: 0.0908 Hom.: 95

Bravo AF: 0.0888

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.76
PhyloP100		-0.36
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: rs2214512; hg19: chr7-8586685;