rs11745562

chr5-32781298-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.1290+482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,148 control chromosomes in the GnomAD database, including 3,794 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 0.22 (3794 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR3	NM_001204375.2	c.1290+482C>T		intron_variant		ENST00000265074.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR3	ENST00000265074.13	c.1290+482C>T		intron_variant		1	NM_001204375.2	P4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33493 AN: 152030 Hom.: 3794 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.220 AC: 33515 AN: 152148 Hom.: 3794 Cov.: 32 AF XY: 0.224 AC XY: 16681 AN XY: 74388

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.189

Alfa AF: 0.213 Hom.: 441

Bravo AF: 0.217

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.66

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: rs11745562; hg19: chr5-32781404;