NM_001204375.2:c.1060-6180A>G

Variant names:

• chr5-32768528-A-G
• rs3792752
• NM_001204375.2:c.1060-6180A>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.1060-6180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,018 control chromosomes in the GnomAD database, including 7,818 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 0.31 (7818 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1060-6180A>G		intron_variant	Intron 3 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1060-6180A>G		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46926 AN: 151900 Hom.: 7816 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.309 AC: 46965 AN: 152018 Hom.: 7818 Cov.: 32 AF XY: 0.305 AC XY: 22667 AN XY: 74292

African (AFR) AF: 0.438 AC: 18160 AN: 41418

American (AMR) AF: 0.294 AC: 4497 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3472

East Asian (EAS) AF: 0.172 AC: 885 AN: 5160

South Asian (SAS) AF: 0.271 AC: 1303 AN: 4812

European-Finnish (FIN) AF: 0.206 AC: 2179 AN: 10586

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17869 AN: 67978

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.277 Hom.: 24716

Bravo AF: 0.317

Asia WGS AF: 0.265 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.48
PhyloP100		0.47
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: rs3792752; hg19: chr5-32768634;