rs7485577

chr12-57222278-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007224.4(NXPH4):c.58-2600G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,058 control chromosomes in the GnomAD database, including 4,188 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 0.21 (4188 hom., cov: 32)
• Consequence: NXPH4 NM_007224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884

Genes affected

NXPH4 (HGNC:8078): (neurexophilin 4) Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPH4	NM_007224.4	c.58-2600G>A		intron_variant		ENST00000349394.6
NXPH4	XM_017018747.2	c.58-2600G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPH4	ENST00000349394.6	c.58-2600G>A		intron_variant		1	NM_007224.4	P1
NXPH4	ENST00000556415.1	c.*184+734G>A		intron_variant, NMD_transcript_variant		2
NXPH4	ENST00000555154.1	n.108+2302G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32602 AN: 151942 Hom.: 4179 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.215 AC: 32617 AN: 152058 Hom.: 4188 Cov.: 32 AF XY: 0.212 AC XY: 15788 AN XY: 74314

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.239

Alfa AF: 0.261 Hom.: 7827

Bravo AF: 0.222

Asia WGS AF: 0.161 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.0
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs7485577; hg19: chr12-57616061;