5-32753566-T-C

Variant names:

• chr5-32753566-T-C
• rs2062708
• NM_001204375.2:c.1059+14536T>C

Variant summary

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

The NM_001204375.2(NPR3):​c.1059+14536T>C 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 151,538 control chromosomes in the GnomAD database, including 2,059 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 (2059 hom., cov: 30)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+14536T>C		intron_variant	Intron 3 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1059+14536T>C		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24293 AN: 151422 Hom.: 2057 Cov.: 30

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.160 AC: 24319 AN: 151538 Hom.: 2059 Cov.: 30 AF XY: 0.161 AC XY: 11915 AN XY: 74000

African (AFR) AF: 0.155 AC: 6422 AN: 41304

American (AMR) AF: 0.198 AC: 3002 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3468

East Asian (EAS) AF: 0.167 AC: 857 AN: 5138

South Asian (SAS) AF: 0.222 AC: 1066 AN: 4812

European-Finnish (FIN) AF: 0.107 AC: 1114 AN: 10404

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10661 AN: 67930

Other (OTH) AF: 0.150 AC: 315 AN: 2102

Alfa AF: 0.142 Hom.: 784

Bravo AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		-0.23
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: rs2062708; hg19: chr5-32753672;