Genetic Variant NM_001204375.2:c.1195+98G>T (chr5-32774941-G-T) – 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.1195+98G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 907,852 control chromosomes in the GnomAD database, including 137,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27615 hom., cov: 32)

Exomes 𝑓: 0.53 ( 110112 hom. )

Consequence

NPR3
NM_001204375.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-32774941-G-T is Benign according to our data. Variant chr5-32774941-G-T is described in ClinVar as [Benign]. Clinvar id is 1222046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2 link	c.1195+98G>T		intron_variant	Intron 4 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.1195+98G>T		intron_variant	Intron 4 of 7	1	NM_001204375.2	ENSP00000265074.8		P17342-1

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90166

AN:

151926

Hom.:

27565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.737

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.577

GnomAD4 exome

AF:

0.534

AC:

403498

AN:

755808

Hom.:

110112

AF XY:

0.537

AC XY:

213308

AN XY:

397422

show subpopulations

Gnomad4 AFR exome

AF:

0.737

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.550

Gnomad4 EAS exome

AF:

0.598

Gnomad4 SAS exome

AF:

0.592

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.594

AC:

90279

AN:

152044

Hom.:

27615

Cov.:

AF XY:

0.596

AC XY:

44298

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.738

Gnomad4 AMR

AF:

0.550

Gnomad4 ASJ

AF:

0.552

Gnomad4 EAS

AF:

0.632

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.549

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.529

Hom.:

8600

Bravo

AF:

0.598

Asia WGS

AF:

0.606

AC:

2106

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.33

DANN

Benign

0.73

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

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