5-32689612-C-G

Variant names:

• chr5-32689612-C-G
• rs6450922
• ENST00000509104.5:c.100+426C>G

Variant summary

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

The ENST00000509104.5(NPR3):​c.100+426C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,188 control chromosomes in the GnomAD database, including 3,994 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 0.21 (3994 hom., cov: 33)
• Consequence: NPR3 ENST00000509104.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000509104.5	c.100+426C>G		intron_variant	Intron 1 of 5	2		ENSP00000425325.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31545 AN: 152070 Hom.: 3992 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.207 AC: 31548 AN: 152188 Hom.: 3994 Cov.: 33 AF XY: 0.210 AC XY: 15590 AN XY: 74396

African (AFR) AF: 0.0624 AC: 2594 AN: 41548

American (AMR) AF: 0.233 AC: 3562 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3468

East Asian (EAS) AF: 0.177 AC: 915 AN: 5178

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4818

European-Finnish (FIN) AF: 0.319 AC: 3370 AN: 10554

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18012 AN: 68008

Other (OTH) AF: 0.205 AC: 434 AN: 2116

Alfa AF: 0.120 Hom.: 237

Bravo AF: 0.194

Asia WGS AF: 0.242 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.75
PhyloP100		-0.14

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6450922; hg19: chr5-32689718;