rs11612037

Positions:

• chr12-57219990-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007224.4(NXPH4):​c.57+2964C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,542 control chromosomes in the GnomAD database, including 133 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 0.033 (132 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1 hom.)
• Consequence: NXPH4 NM_007224.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.033 (5023/152196) while in subpopulation NFE AF= 0.0511 (3476/68000). AF 95% confidence interval is 0.0497. There are 132 homozygotes in gnomad4. There are 2403 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 132 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXPH4	NM_007224.4	c.57+2964C>T		intron_variant		ENST00000349394.6
NXPH4	XM_017018747.2	c.57+2964C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXPH4	ENST00000349394.6	c.57+2964C>T		intron_variant		1	NM_007224.4	P1
NXPH4	ENST00000556415.1	c.58-1317C>T		intron_variant, NMD_transcript_variant		2
NXPH4	ENST00000555154.1	n.108+14C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5023 AN: 152078 Hom.: 132 Cov.: 33

Gnomad AFR AF: 0.00800

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0434 AC: 15 AN: 346 Hom.: 1 Cov.: 0 AF XY: 0.0413 AC XY: 9 AN XY: 218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0545

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0330 AC: 5023 AN: 152196 Hom.: 132 Cov.: 33 AF XY: 0.0323 AC XY: 2403 AN XY: 74406

Gnomad4 AFR AF: 0.00795

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0463

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0460 Hom.: 170

Bravo AF: 0.0314

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11612037; hg19: chr12-57613773;