Genetic Variant NPR3:c.-250C>A (chr5-32711527-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001204375.2(NPR3):c.-250C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,199,638 control chromosomes in the GnomAD database, including 20,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1745 hom., cov: 30)

Exomes 𝑓: 0.18 ( 18463 hom. )

Consequence

NPR3
NM_001204375.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.685

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 5-32711527-C-A is Benign according to our data. Variant chr5-32711527-C-A is described in ClinVar as [Benign]. Clinvar id is 1177755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2 link	c.-250C>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000265074.13	NP_001191304.1	P17342-1A8K4A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074 link	c.-250C>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_001204375.2	ENSP00000265074.8		P17342-1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20022

AN:

149838

Hom.:

1745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0361

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.000987

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.103

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.181

AC:

190449

AN:

1049700

Hom.:

18463

Cov.:

AF XY:

0.181

AC XY:

89675

AN XY:

494978

show subpopulations

Gnomad4 AFR exome

AF:

0.0249

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.000869

Gnomad4 SAS exome

AF:

0.0813

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.133

AC:

20009

AN:

149938

Hom.:

1745

Cov.:

AF XY:

0.131

AC XY:

9564

AN XY:

73074

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.000989

Gnomad4 SAS

AF:

0.0738

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.153

Hom.:

294

Bravo

AF:

0.127

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10489108) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.86

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over