dbSNP rs10057069: NPR3:c.769+3938T>C (chr5-32716483-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.359

Publications

5 publications found

Variant links:

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)

NPR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2 link	c.769+3938T>C		intron_variant	Intron 1 of 7	ENST00000265074.13	NP_001191304.1	P17342-1A8K4A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13 link	c.769+3938T>C		intron_variant	Intron 1 of 7	1	NM_001204375.2	ENSP00000265074.8		P17342-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34405

AN:

151972

Hom.:

4174

Cov.:

show subpopulations

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.:

AF XY:

0.213

AC XY:

36020

AN XY:

168874

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

2272

4544

6815

9087

11359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34399

AN:

152090

Hom.:

4167

Cov.:

AF XY:

0.221

AC XY:

16412

AN XY:

74338

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1326

2652

3977

5303

6629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

(source)

DANN

Benign

0.55

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over