5-32744923-C-T

Variant names:

• chr5-32744923-C-T
• rs700925
• NM_001204375.2:c.1059+5893C>T

Variant summary

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

The ENST00000265074.13(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 ENST00000265074.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265074.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	NM_001204375.2	MANE Select	c.1059+5893C>T		intron	N/A	NP_001191304.1
	NPR3	NM_000908.4		c.1059+5893C>T		intron	N/A	NP_000899.1
	NPR3	NM_001363652.2		c.411+5893C>T		intron	N/A	NP_001350581.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	ENST00000265074.13	TSL:1 MANE Select	c.1059+5893C>T		intron	N/A	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.1059+5893C>T		intron	N/A	ENSP00000398028.2
	NPR3	ENST00000506712.1	TSL:1	n.420+5893C>T		intron	N/A

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

African (AFR) AF: 0.297 AC: 12328 AN: 41490

American (AMR) AF: 0.248 AC: 3788 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1295 AN: 5176

South Asian (SAS) AF: 0.246 AC: 1188 AN: 4828

European-Finnish (FIN) AF: 0.164 AC: 1736 AN: 10588

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13023 AN: 67996

Other (OTH) AF: 0.201 AC: 423 AN: 2104

Alfa AF: 0.200 Hom.: 5343

Bravo AF: 0.236

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.32
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: rs700925; hg19: chr5-32745029;