rs696836

chr5-32734302-T-G

Variant summary

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

The NM_001204375.2(NPR3):c.893-4562T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,124 control chromosomes in the GnomAD database, including 1,778 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 0.13 (1778 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001204375.2	c.893-4562T>G		intron_variant		ENST00000265074.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000265074.13	c.893-4562T>G		intron_variant		1	NM_001204375.2	P4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20517 AN: 152006 Hom.: 1779 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.135 AC: 20515 AN: 152124 Hom.: 1778 Cov.: 32 AF XY: 0.131 AC XY: 9733 AN XY: 74378

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0916

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.158

Alfa AF: 0.111 Hom.: 1456

Bravo AF: 0.140

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.62
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: rs696836; hg19: chr5-32734408;