5-32750877-T-C

Position:

• chr5-32750877-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265074.13(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 ENST00000265074.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+11847T>C		intron_variant		ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1059+11847T>C		intron_variant		1	NM_001204375.2	ENSP00000265074	P4

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

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.410

Alfa AF: 0.349 Hom.: 4422

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

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: rs1173773; hg19: chr5-32750983;