NM_001204375.2:c.1195+1066T>A

Variant names:

• chr5-32775909-T-A
• rs6864434
• NM_001204375.2:c.1195+1066T>A

Variant summary

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

The NM_001204375.2(NPR3):​c.1195+1066T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,032 control chromosomes in the GnomAD database, including 13,240 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 0.41 (13240 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1195+1066T>A		intron_variant	Intron 4 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1195+1066T>A		intron_variant	Intron 4 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62344 AN: 151914 Hom.: 13217 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.388

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62422 AN: 152032 Hom.: 13240 Cov.: 32 AF XY: 0.419 AC XY: 31122 AN XY: 74334

African (AFR) AF: 0.341 AC: 14147 AN: 41452

American (AMR) AF: 0.439 AC: 6710 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3239 AN: 5174

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4820

European-Finnish (FIN) AF: 0.453 AC: 4789 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28172 AN: 67948

Other (OTH) AF: 0.393 AC: 831 AN: 2112

Alfa AF: 0.397 Hom.: 1514

Bravo AF: 0.405

Asia WGS AF: 0.557 AC: 1936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.65
PhyloP100		-0.13
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: rs6864434; hg19: chr5-32776015;