5-32739555-A-G

Variant names:

• chr5-32739555-A-G
• rs16890196
• NM_001204375.2:c.1059+525A>G

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+525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,026 control chromosomes in the GnomAD database, including 2,880 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 0.19 (2880 hom., cov: 31)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+525A>G		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+525A>G		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29220 AN: 151908 Hom.: 2876 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.192 AC: 29249 AN: 152026 Hom.: 2880 Cov.: 31 AF XY: 0.194 AC XY: 14421 AN XY: 74306

African (AFR) AF: 0.170 AC: 7046 AN: 41448

American (AMR) AF: 0.237 AC: 3626 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1259 AN: 5162

South Asian (SAS) AF: 0.260 AC: 1252 AN: 4812

European-Finnish (FIN) AF: 0.165 AC: 1745 AN: 10570

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12989 AN: 67978

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.117 Hom.: 248

Bravo AF: 0.194

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	-0.86
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.33
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: rs16890196; hg19: chr5-32739661;