dbSNP rs572035979: NPR3:n.27G>A (chr5-32710680-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001363652.2(NPR3):c.18G>A(p.Leu6Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000584 in 1,540,660 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 11 hom. )

Consequence

NPR3
NM_001363652.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.106

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 5-32710680-G-A is Benign according to our data. Variant chr5-32710680-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058216.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.106 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363652.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPR3	NM_001363652.2	c.18G>A	p.Leu6Leu	synonymous	Exon 1 of 8	NP_001350581.1	C9JK69
NPR3	NM_001204376.2	c.18G>A	p.Leu6Leu	synonymous	Exon 1 of 8	NP_001191305.1	P17342-3
NPR3	NM_001364460.2	c.18G>A	p.Leu6Leu	synonymous	Exon 1 of 7	NP_001351389.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPR3	ENST00000506712.1	TSL:1	n.27G>A		non_coding_transcript_exon	Exon 1 of 6
NPR3	ENST00000434067.6	TSL:5	c.18G>A	p.Leu6Leu	synonymous	Exon 1 of 8	ENSP00000388408.2	C9JK69
NPR3	ENST00000326958.5	TSL:2	c.18G>A	p.Leu6Leu	synonymous	Exon 1 of 8	ENSP00000318340.2	P17342-3

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00163

AC:

225

AN:

137864

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000454

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000508

GnomAD4 exome

AF:

0.000608

AC:

844

AN:

1388366

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

606

AN XY:

684256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31018

American (AMR)

AF:

0.0000293

AC:

AN:

34136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24942

East Asian (EAS)

AF:

0.00

AC:

AN:

35204

South Asian (SAS)

AF:

0.0104

AC:

804

AN:

77042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48032

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.00000372

AC:

AN:

1074694

Other (OTH)

AF:

0.000590

AC:

AN:

57632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000361

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.0110

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000171

Hom.:

Bravo

AF:

0.0000416

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NPR3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.8

(source)

DANN

Benign

0.74

PhyloP100

0.11

PromoterAI

-0.032

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over