chr5-32761323-C-T

Variant names:

• chr5-32761323-C-T
• rs11749888
• NM_001204375.2:c.1060-13385C>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.1060-13385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,006 control chromosomes in the GnomAD database, including 1,520 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 (1520 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 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.1060-13385C>T		intron	N/A	NP_001191304.1	P17342-1
	NPR3	NM_000908.4		c.1060-13385C>T		intron	N/A	NP_000899.1	P17342-2
	NPR3	NM_001363652.2		c.412-13385C>T		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.1060-13385C>T		intron	N/A	ENSP00000265074.8	P17342-1
	NPR3	ENST00000415167.2	TSL:1	c.1060-13385C>T		intron	N/A	ENSP00000398028.2	P17342-2
	NPR3	ENST00000506712.1	TSL:1	n.421-13385C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20781 AN: 151888 Hom.: 1521 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.137 AC: 20800 AN: 152006 Hom.: 1520 Cov.: 32 AF XY: 0.140 AC XY: 10372 AN XY: 74304

African (AFR) AF: 0.175 AC: 7236 AN: 41450

American (AMR) AF: 0.167 AC: 2555 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3464

East Asian (EAS) AF: 0.170 AC: 877 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4812

European-Finnish (FIN) AF: 0.0888 AC: 937 AN: 10550

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7230 AN: 67976

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.122 Hom.: 147

Bravo AF: 0.141

Asia WGS AF: 0.220 AC: 762 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.31
PhyloP100		0.18
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: rs11749888; hg19: chr5-32761429;