rs696836

Variant names:

• chr5-32734302-T-G
• rs696836
• NM_001204375.2:c.893-4562T>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.893-4562T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,124 control chromosomes in the GnomAD database, including 1,778 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 0.13 (1778 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204375.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	NM_001204375.2	MANE Select	c.893-4562T>G		intron	N/A	NP_001191304.1	P17342-1
	NPR3	NM_000908.4		c.893-4562T>G		intron	N/A	NP_000899.1	P17342-2
	NPR3	NM_001363652.2		c.245-4562T>G		intron	N/A	NP_001350581.1	C9JK69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	ENST00000265074.13	TSL:1 MANE Select	c.893-4562T>G		intron	N/A	ENSP00000265074.8	P17342-1
	NPR3	ENST00000415167.2	TSL:1	c.893-4562T>G		intron	N/A	ENSP00000398028.2	P17342-2
	NPR3	ENST00000506712.1	TSL:1	n.254-4562T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20517 AN: 152006 Hom.: 1779 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0708

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.135 AC: 20515 AN: 152124 Hom.: 1778 Cov.: 32 AF XY: 0.131 AC XY: 9733 AN XY: 74378

African (AFR) AF: 0.239 AC: 9930 AN: 41468

American (AMR) AF: 0.0916 AC: 1401 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0696 AC: 335 AN: 4814

European-Finnish (FIN) AF: 0.0834 AC: 884 AN: 10604

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7077 AN: 67970

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.115 Hom.: 2006

Bravo AF: 0.140

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.64
PhyloP100		-1.5
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: rs696836; hg19: chr5-32734408;