rs11749888

Positions:

• chr5-32761323-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.1060-13385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,006 control chromosomes in the GnomAD database, including 1,520 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 0.14 (1520 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1060-13385C>T		intron_variant		ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1060-13385C>T		intron_variant		1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20781 AN: 151888 Hom.: 1521 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.137 AC: 20800 AN: 152006 Hom.: 1520 Cov.: 32 AF XY: 0.140 AC XY: 10372 AN XY: 74304

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.120

Alfa AF: 0.119 Hom.: 134

Bravo AF: 0.141

Asia WGS AF: 0.220 AC: 762 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.31

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: rs11749888; hg19: chr5-32761429;