rs11740580

Positions:

• chr5-32765351-C-A
• chr5-32765351-C-G
• chr5-32765351-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001204375.2(NPR3):​c.1060-9357C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,246 control chromosomes in the GnomAD database, including 134 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 0.039 (134 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0389 (5918/152246) while in subpopulation NFE AF= 0.0464 (3156/68018). AF 95% confidence interval is 0.045. There are 134 homozygotes in gnomad4. There are 2774 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5918 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1060-9357C>A		intron_variant		ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1060-9357C>A		intron_variant		1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5910 AN: 152128 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0389 AC: 5918 AN: 152246 Hom.: 134 Cov.: 32 AF XY: 0.0373 AC XY: 2774 AN XY: 74458

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.0351

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0464

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0398 Hom.: 182

Bravo AF: 0.0388

Asia WGS AF: 0.00895 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.87
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs11740580; hg19: chr5-32765457;