NM_001204375.2:c.1060-2771A>G

Variant names:

• chr5-32771937-A-G
• rs3811958
• NM_001204375.2:c.1060-2771A>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.1060-2771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,680 control chromosomes in the GnomAD database, including 9,662 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 0.33 (9662 hom., cov: 30)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1060-2771A>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.1060-2771A>G		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50680 AN: 151560 Hom.: 9647 Cov.: 30

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.335 AC: 50747 AN: 151680 Hom.: 9662 Cov.: 30 AF XY: 0.331 AC XY: 24546 AN XY: 74142

African (AFR) AF: 0.530 AC: 21893 AN: 41290

American (AMR) AF: 0.301 AC: 4591 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 966 AN: 3462

East Asian (EAS) AF: 0.171 AC: 879 AN: 5140

South Asian (SAS) AF: 0.271 AC: 1297 AN: 4790

European-Finnish (FIN) AF: 0.205 AC: 2154 AN: 10528

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17821 AN: 67924

Other (OTH) AF: 0.337 AC: 706 AN: 2096

Alfa AF: 0.286 Hom.: 3675

Bravo AF: 0.347

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		2.0
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: rs3811958; hg19: chr5-32772043;