NM_001204375.2:c.769+1619C>G

Variant names:

• chr5-32714164-C-G
• rs1421811
• NM_001204375.2:c.769+1619C>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.769+1619C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,860 control chromosomes in the GnomAD database, including 10,092 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 0.36 (10092 hom., cov: 34)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 19 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 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+1619C>G		intron	N/A	NP_001191304.1
	NPR3	NM_000908.4		c.769+1619C>G		intron	N/A	NP_000899.1
	NPR3	NM_001363652.2		c.121+3381C>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.769+1619C>G		intron	N/A	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.769+1619C>G		intron	N/A	ENSP00000398028.2
	NPR3	ENST00000506712.1	TSL:1	n.130+3381C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54257 AN: 151740 Hom.: 10092 Cov.: 34

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.357 AC: 54284 AN: 151860 Hom.: 10092 Cov.: 34 AF XY: 0.353 AC XY: 26212 AN XY: 74216

African (AFR) AF: 0.339 AC: 14045 AN: 41392

American (AMR) AF: 0.385 AC: 5873 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1350 AN: 3470

East Asian (EAS) AF: 0.110 AC: 564 AN: 5114

South Asian (SAS) AF: 0.191 AC: 920 AN: 4812

European-Finnish (FIN) AF: 0.361 AC: 3814 AN: 10556

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26566 AN: 67930

Other (OTH) AF: 0.360 AC: 760 AN: 2114

Alfa AF: 0.242 Hom.: 581

Bravo AF: 0.359

Asia WGS AF: 0.148 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.059
DANN	Benign	0.37
PhyloP100		-1.7
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: rs1421811; hg19: chr5-32714270; COSMIC: COSV54093582;