NM_001204375.2:c.1059+1848G>A

Variant names:

• chr5-32740878-G-A
• rs16890208
• NM_001204375.2:c.1059+1848G>A

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+1848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 150,874 control chromosomes in the GnomAD database, including 1,397 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 (1397 hom., cov: 31)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 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.1059+1848G>A		intron	N/A	NP_001191304.1
	NPR3	NM_000908.4		c.1059+1848G>A		intron	N/A	NP_000899.1
	NPR3	NM_001363652.2		c.411+1848G>A		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.1059+1848G>A		intron	N/A	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.1059+1848G>A		intron	N/A	ENSP00000398028.2
	NPR3	ENST00000506712.1	TSL:1	n.420+1848G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19973 AN: 150756 Hom.: 1393 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.133 AC: 19995 AN: 150874 Hom.: 1397 Cov.: 31 AF XY: 0.136 AC XY: 10025 AN XY: 73662

African (AFR) AF: 0.126 AC: 5176 AN: 41194

American (AMR) AF: 0.166 AC: 2500 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 430 AN: 3450

East Asian (EAS) AF: 0.218 AC: 1102 AN: 5056

South Asian (SAS) AF: 0.220 AC: 1042 AN: 4736

European-Finnish (FIN) AF: 0.128 AC: 1329 AN: 10414

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7894 AN: 67686

Other (OTH) AF: 0.117 AC: 244 AN: 2090

Alfa AF: 0.129 Hom.: 213

Bravo AF: 0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.63
PhyloP100		0.29
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: rs16890208; hg19: chr5-32740984;