rs5268

Positions:

• chr2-231925343-C-T

Variant summary

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

The NM_024409.4(NPPC):​c.*20+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,357,522 control chromosomes in the GnomAD database, including 252,140 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 0.55 (23654 hom., cov: 34)
  • Exomes 𝑓: 0.61 (228486 hom.)
• Consequence: NPPC NM_024409.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

NPPC (HGNC:7941): (natriuretic peptide C) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cardiac natriuretic peptides CNP-53, CNP-29 and CNP-22, which belong to the natriuretic family of peptides. The encoded peptides exhibit vasorelaxation activity in laboratory animals and elevated levels of CNP-22 have been observed in the plasma of chronic heart failure patients. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPPC	NM_024409.4	c.*20+62G>A		intron_variant		ENST00000409852.2
NPPC	XM_011511245.4	c.*20+62G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPPC	ENST00000409852.2	c.*20+62G>A		intron_variant		3	NM_024409.4	P1
NPPC	ENST00000295440.2			downstream_gene_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83170 AN: 152014 Hom.: 23650 Cov.: 34

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.609 AC: 733828 AN: 1205394 Hom.: 228486 Cov.: 20 AF XY: 0.606 AC XY: 354477 AN XY: 584532

Gnomad4 AFR exome AF: 0.481

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.547 AC: 83201 AN: 152128 Hom.: 23654 Cov.: 34 AF XY: 0.541 AC XY: 40227 AN XY: 74368

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.541

Alfa AF: 0.595 Hom.: 3431

Bravo AF: 0.525

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Uncertain	0.98

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: rs5268; hg19: chr2-232790053;