rs9716700

Positions:

• chr5-32711527-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204375.2(NPR3):​c.-250C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,199,638 control chromosomes in the GnomAD database, including 20,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1745 hom., cov: 30)
  • Exomes 𝑓: 0.18 (18463 hom.)
• Consequence: NPR3 NM_001204375.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.685

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]

NPR3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 5-32711527-C-A is Benign according to our data. Variant chr5-32711527-C-A is described in ClinVar as [Benign]. Clinvar id is 1177755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.-250C>A		5_prime_UTR_variant	1/8	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074	c.-250C>A		5_prime_UTR_variant	1/8	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20022 AN: 149838 Hom.: 1745 Cov.: 30

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000987

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.181 AC: 190449 AN: 1049700 Hom.: 18463 Cov.: 20 AF XY: 0.181 AC XY: 89675 AN XY: 494978

Gnomad4 AFR exome AF: 0.0249

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.000869

Gnomad4 SAS exome AF: 0.0813

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.133 AC: 20009 AN: 149938 Hom.: 1745 Cov.: 30 AF XY: 0.131 AC XY: 9564 AN XY: 73074

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000989

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.145

Alfa AF: 0.153 Hom.: 294

Bravo AF: 0.127

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	This variant is associated with the following publications: (PMID: 10489108) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9716700; hg19: chr5-32711633;