5-32710655-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000506712.1(NPR3):n.2G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,501,148 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (359 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (262 hom.)
• Consequence: NPR3 ENST00000506712.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 5-32710655-G-A is Benign according to our data. Variant chr5-32710655-G-A is described in ClinVar as [Benign]. Clinvar id is 3044637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001204376.2	c.-8G>A		5_prime_UTR_variant	1/8
NPR3	NM_001363652.2	c.-8G>A		5_prime_UTR_variant	1/8
NPR3	NM_001364460.2	c.-8G>A		5_prime_UTR_variant	1/7
NPR3	NM_001364458.2	c.50-14043G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000506712.1	n.2G>A		non_coding_transcript_exon_variant	1/6	1
NPR3	ENST00000326958.5	c.-8G>A		5_prime_UTR_variant	1/8	2
NPR3	ENST00000434067.6	c.-8G>A		5_prime_UTR_variant	1/8	5
NPR3	ENST00000509104.5	c.101-14043G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5605 AN: 152080 Hom.: 359 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00922

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00709 AC: 814 AN: 114874 Hom.: 46 AF XY: 0.00568 AC XY: 351 AN XY: 61776

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.00571

Gnomad ASJ exome AF: 0.000150

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000188

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000162

Gnomad OTH exome AF: 0.00483

GnomAD4 exome AF: 0.00343 AC: 4633 AN: 1348950 Hom.: 262 Cov.: 31 AF XY: 0.00297 AC XY: 1961 AN XY: 660084

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.00658

Gnomad4 ASJ exome AF: 0.0000426

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000779

Gnomad4 OTH exome AF: 0.00773

GnomAD4 genome AF: 0.0369 AC: 5611 AN: 152198 Hom.: 359 Cov.: 32 AF XY: 0.0346 AC XY: 2575 AN XY: 74434

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.00914

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0181 Hom.: 69

Bravo AF: 0.0419

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NPR3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	16
Dann	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28513089; hg19: chr5-32710761;