5-32740240-G-T

Variant names:

• chr5-32740240-G-T
• rs10066436
• NM_001204375.2:c.1059+1210G>T

Variant summary

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

The NM_001204375.2(NPR3):​c.1059+1210G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,122 control chromosomes in the GnomAD database, including 2,285 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 0.17 (2285 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 2 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 (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1059+1210G>T		intron_variant	Intron 3 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1059+1210G>T		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25879 AN: 152002 Hom.: 2282 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.170 AC: 25916 AN: 152122 Hom.: 2285 Cov.: 32 AF XY: 0.174 AC XY: 12916 AN XY: 74382

African (AFR) AF: 0.175 AC: 7278 AN: 41500

American (AMR) AF: 0.198 AC: 3034 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1188 AN: 5158

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10592

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10267 AN: 67972

Other (OTH) AF: 0.161 AC: 340 AN: 2112

Alfa AF: 0.134 Hom.: 556

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.52
PhyloP100		-0.032
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: rs10066436; hg19: chr5-32740346;