rs764124

chr5-32709113-G-A

Variant summary

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

The NM_001364458.2(NPR3):c.50-15585G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,928 control chromosomes in the GnomAD database, including 3,237 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 0.20 (3237 hom., cov: 30)
• Consequence: NPR3 NM_001364458.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

Genes affected

NPR3 (HGNC:7945): (natriuretic peptide receptor 3) This gene encodes one of three natriuretic peptide receptors. Natriutetic peptides are small peptides which regulate blood volume and pressure, pulmonary hypertension, and cardiac function as well as some metabolic and growth processes. The product of this gene encodes a natriuretic peptide receptor responsible for clearing circulating and extracellular natriuretic peptides through endocytosis of the receptor. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001364458.2	c.50-15585G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000509104.5	c.101-15585G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30074 AN: 151810 Hom.: 3242 Cov.: 30

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.198 AC: 30054 AN: 151928 Hom.: 3237 Cov.: 30 AF XY: 0.195 AC XY: 14477 AN XY: 74266

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.225

Alfa AF: 0.219 Hom.: 965

Bravo AF: 0.190

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs764124; hg19: chr5-32709219;