rs4334435

Variant names:

• chr2-138747565-T-C
• rs4334435
• NM_007226.3:c.51+32626A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007226.3(NXPH2):​c.51+32626A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 152,238 control chromosomes in the GnomAD database, including 67,563 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 0.94 (67563 hom., cov: 32)
• Consequence: NXPH2 NM_007226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 2 publications found

Genes affected

NXPH2 (HGNC:8076): (neurexophilin 2) Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH2	NM_007226.3	c.51+32626A>G		intron_variant	Intron 1 of 1	ENST00000272641.4	NP_009157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXPH2	ENST00000272641.4	c.51+32626A>G		intron_variant	Intron 1 of 1	1	NM_007226.3	ENSP00000272641.3

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142678 AN: 152120 Hom.: 67526 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.987

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.949

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

GnomAD4 genome AF: 0.938 AC: 142768 AN: 152238 Hom.: 67563 Cov.: 32 AF XY: 0.939 AC XY: 69882 AN XY: 74418

African (AFR) AF: 0.803 AC: 33336 AN: 41524

American (AMR) AF: 0.974 AC: 14895 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3470 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4675 AN: 5168

South Asian (SAS) AF: 0.987 AC: 4757 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10622

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67811 AN: 68024

Other (OTH) AF: 0.949 AC: 2004 AN: 2112

Alfa AF: 0.977 Hom.: 85070

Bravo AF: 0.929

Asia WGS AF: 0.947 AC: 3292 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.047
DANN	Benign	0.58
PhyloP100		-2.3
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: rs4334435; hg19: chr2-139505135;