5-32744923-C-T

Position:

• chr5-32744923-C-T

Variant summary

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

The NM_001204375.2(NPR3):​c.1059+5893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,134 control chromosomes in the GnomAD database, including 4,149 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 0.23 (4149 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+5893C>T		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+5893C>T		intron_variant		1	NM_001204375.2	ENSP00000265074	P4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34715 AN: 152018 Hom.: 4143 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.228 AC: 34757 AN: 152134 Hom.: 4149 Cov.: 32 AF XY: 0.229 AC XY: 17038 AN XY: 74388

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.201

Alfa AF: 0.196 Hom.: 4064

Bravo AF: 0.236

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.51

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: rs700925; hg19: chr5-32745029;