chr5-32734034-A-G

Variant names:

• chr5-32734034-A-G
• rs1833529
• NM_001204375.2:c.893-4830A>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.893-4830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,198 control chromosomes in the GnomAD database, including 1,485 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 0.14 (1485 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 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.893-4830A>G		intron	N/A	NP_001191304.1
	NPR3	NM_000908.4		c.893-4830A>G		intron	N/A	NP_000899.1
	NPR3	NM_001363652.2		c.245-4830A>G		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.893-4830A>G		intron	N/A	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.893-4830A>G		intron	N/A	ENSP00000398028.2
	NPR3	ENST00000506712.1	TSL:1	n.254-4830A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20611 AN: 152080 Hom.: 1479 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.136 AC: 20641 AN: 152198 Hom.: 1485 Cov.: 32 AF XY: 0.140 AC XY: 10429 AN XY: 74424

African (AFR) AF: 0.126 AC: 5221 AN: 41516

American (AMR) AF: 0.174 AC: 2662 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1187 AN: 5180

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4820

European-Finnish (FIN) AF: 0.135 AC: 1426 AN: 10598

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8078 AN: 68014

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.0599 Hom.: 57

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
DANN	Benign	0.83
PhyloP100		-0.22
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: rs1833529; hg19: chr5-32734140;