rs2302954

Variant names:

• chr5-32735013-T-A
• rs2302954
• NM_001204375.2:c.893-3851T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204375.2(NPR3):​c.893-3851T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,186 control chromosomes in the GnomAD database, including 2,013 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 0.16 (2013 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Boudin-Mortier syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.893-3851T>A		intron_variant	Intron 2 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.893-3851T>A		intron_variant	Intron 2 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24264 AN: 152066 Hom.: 2015 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.160 AC: 24281 AN: 152186 Hom.: 2013 Cov.: 32 AF XY: 0.163 AC XY: 12108 AN XY: 74406

African (AFR) AF: 0.138 AC: 5713 AN: 41532

American (AMR) AF: 0.196 AC: 2996 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1182 AN: 5156

South Asian (SAS) AF: 0.276 AC: 1332 AN: 4824

European-Finnish (FIN) AF: 0.143 AC: 1520 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10250 AN: 68004

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.152 Hom.: 222

Bravo AF: 0.160

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.4
DANN	Benign	0.92
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2302954; hg19: chr5-32735119;