rs1421811

chr5-32714164-C-Gchr5-32714164-C-T

Variant summary

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

The NM_001204375.2(NPR3):c.769+1619C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,860 control chromosomes in the GnomAD database, including 10,092 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 0.36 (10092 hom., cov: 34)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001204375.2	c.769+1619C>G		intron_variant		ENST00000265074.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000265074.13	c.769+1619C>G		intron_variant		1	NM_001204375.2	P4

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54257 AN: 151740 Hom.: 10092 Cov.: 34

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.357 AC: 54284 AN: 151860 Hom.: 10092 Cov.: 34 AF XY: 0.353 AC XY: 26212 AN XY: 74216

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.360

Alfa AF: 0.242 Hom.: 581

Bravo AF: 0.359

Asia WGS AF: 0.148 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.059
Dann	Benign	0.37

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: rs1421811; hg19: chr5-32714270; COSMIC: COSV54093582;