NM_001204375.2:c.1059+11847T>C

Variant names:

• chr5-32750877-T-C
• rs1173773
• NM_001204375.2:c.1059+11847T>C

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+11847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,068 control chromosomes in the GnomAD database, including 13,998 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 0.41 (13998 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+11847T>C		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.1059+11847T>C		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61616 AN: 151950 Hom.: 13969 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.406 AC: 61693 AN: 152068 Hom.: 13998 Cov.: 32 AF XY: 0.399 AC XY: 29645 AN XY: 74346

African (AFR) AF: 0.626 AC: 25928 AN: 41448

American (AMR) AF: 0.364 AC: 5566 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3466

East Asian (EAS) AF: 0.192 AC: 993 AN: 5184

South Asian (SAS) AF: 0.335 AC: 1614 AN: 4824

European-Finnish (FIN) AF: 0.252 AC: 2662 AN: 10580

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22298 AN: 67972

Other (OTH) AF: 0.410 AC: 865 AN: 2108

Alfa AF: 0.349 Hom.: 4931

Bravo AF: 0.421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		-0.069
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: rs1173773; hg19: chr5-32750983;