rs10057069

chr5-32716483-T-C

Variant summary

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

The NM_001204375.2(NPR3):c.769+3938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 447,850 control chromosomes in the GnomAD database, including 12,225 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 0.23 (4167 hom., cov: 32)
  • Exomes 𝑓: 0.22 (8058 hom.)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001204375.2	c.769+3938T>C		intron_variant		ENST00000265074.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000265074.13	c.769+3938T>C		intron_variant		1	NM_001204375.2	P4

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34405 AN: 151972 Hom.: 4174 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.219 AC: 64862 AN: 295760 Hom.: 8058 Cov.: 0 AF XY: 0.213 AC XY: 36020 AN XY: 168874

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.000983

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.226 AC: 34399 AN: 152090 Hom.: 4167 Cov.: 32 AF XY: 0.221 AC XY: 16412 AN XY: 74338

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.245

Alfa AF: 0.259 Hom.: 10958

Bravo AF: 0.222

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.55

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: rs10057069; hg19: chr5-32716589;