rs11745562

Variant names:

• chr5-32781298-C-T
• rs11745562
• NM_001204375.2:c.1290+482C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204375.2(NPR3):​c.1290+482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,148 control chromosomes in the GnomAD database, including 3,794 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 0.22 (3794 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1290+482C>T		intron_variant	Intron 5 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1290+482C>T		intron_variant	Intron 5 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33493 AN: 152030 Hom.: 3794 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.220 AC: 33515 AN: 152148 Hom.: 3794 Cov.: 32 AF XY: 0.224 AC XY: 16681 AN XY: 74388

African (AFR) AF: 0.226 AC: 9387 AN: 41482

American (AMR) AF: 0.236 AC: 3608 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1053 AN: 5178

South Asian (SAS) AF: 0.304 AC: 1465 AN: 4820

European-Finnish (FIN) AF: 0.227 AC: 2406 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14349 AN: 68006

Other (OTH) AF: 0.189 AC: 399 AN: 2112

Alfa AF: 0.213 Hom.: 441

Bravo AF: 0.217

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		0.16
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: rs11745562; hg19: chr5-32781404;