rs1847018

Variant names:

• chr5-32714555-C-T
• rs1847018
• NM_001204375.2:c.769+2010C>T

Variant summary

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

The NM_001204375.2(NPR3):​c.769+2010C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 150,024 control chromosomes in the GnomAD database, including 1,210 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 0.12 (1210 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.720
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	NM_001204375.2	MANE Select	c.769+2010C>T		intron	N/A	NP_001191304.1
	NPR3	NM_000908.4		c.769+2010C>T		intron	N/A	NP_000899.1
	NPR3	NM_001363652.2		c.121+3772C>T		intron	N/A	NP_001350581.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	ENST00000265074.13	TSL:1 MANE Select	c.769+2010C>T		intron	N/A	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.769+2010C>T		intron	N/A	ENSP00000398028.2
	NPR3	ENST00000506712.1	TSL:1	n.130+3772C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18565 AN: 149920 Hom.: 1207 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.124 AC: 18579 AN: 150024 Hom.: 1210 Cov.: 32 AF XY: 0.125 AC XY: 9147 AN XY: 73050

African (AFR) AF: 0.109 AC: 4435 AN: 40782

American (AMR) AF: 0.202 AC: 3053 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3462

East Asian (EAS) AF: 0.107 AC: 546 AN: 5104

South Asian (SAS) AF: 0.0839 AC: 400 AN: 4766

European-Finnish (FIN) AF: 0.119 AC: 1173 AN: 9818

Middle Eastern (MID) AF: 0.131 AC: 38 AN: 290

European-Non Finnish (NFE) AF: 0.122 AC: 8227 AN: 67686

Other (OTH) AF: 0.110 AC: 230 AN: 2082

Alfa AF: 0.128 Hom.: 229

Bravo AF: 0.129

Asia WGS AF: 0.0840 AC: 295 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.70
PhyloP100		0.72
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: rs1847018; hg19: chr5-32714661;