rs10057069

Variant names:

• chr5-32716483-T-C
• rs10057069
• NM_001204375.2:c.769+3938T>C

Variant summary

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

The NM_001204375.2(NPR3):​c.769+3938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 447,850 control chromosomes in the GnomAD database, including 12,225 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 (4167 hom., cov: 32)
  • Exomes 𝑓: 0.22 (8058 hom.)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204375.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	NM_001204375.2	MANE Select	c.769+3938T>C		intron	N/A	NP_001191304.1
	NPR3	NM_000908.4		c.769+3938T>C		intron	N/A	NP_000899.1
	NPR3	NM_001363652.2		c.121+5700T>C		intron	N/A	NP_001350581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR3	ENST00000265074.13	TSL:1 MANE Select	c.769+3938T>C		intron	N/A	ENSP00000265074.8
	NPR3	ENST00000415167.2	TSL:1	c.769+3938T>C		intron	N/A	ENSP00000398028.2
	NPR3	ENST00000506712.1	TSL:1	n.130+5700T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34405 AN: 151972 Hom.: 4174 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.219 AC: 64862 AN: 295760 Hom.: 8058 Cov.: 0 AF XY: 0.213 AC XY: 36020 AN XY: 168874

African (AFR) AF: 0.206 AC: 1639 AN: 7962

American (AMR) AF: 0.131 AC: 3295 AN: 25060

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 3032 AN: 10490

East Asian (EAS) AF: 0.000983 AC: 9 AN: 9158

South Asian (SAS) AF: 0.123 AC: 7074 AN: 57580

European-Finnish (FIN) AF: 0.239 AC: 2928 AN: 12228

Middle Eastern (MID) AF: 0.333 AC: 908 AN: 2728

European-Non Finnish (NFE) AF: 0.273 AC: 42714 AN: 156678

Other (OTH) AF: 0.235 AC: 3263 AN: 13876

GnomAD4 genome AF: 0.226 AC: 34399 AN: 152090 Hom.: 4167 Cov.: 32 AF XY: 0.221 AC XY: 16412 AN XY: 74338

African (AFR) AF: 0.204 AC: 8471 AN: 41480

American (AMR) AF: 0.181 AC: 2770 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5178

South Asian (SAS) AF: 0.107 AC: 516 AN: 4824

European-Finnish (FIN) AF: 0.240 AC: 2536 AN: 10560

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18354 AN: 67976

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.254 Hom.: 16150

Bravo AF: 0.222

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-0.36
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: rs10057069; hg19: chr5-32716589;