NM_001204375.2:c.770-5111C>T

Variant names:

• chr5-32719587-C-T
• rs6889608
• NM_001204375.2:c.770-5111C>T

Variant summary

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

The NM_001204375.2(NPR3):​c.770-5111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,996 control chromosomes in the GnomAD database, including 38,879 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 0.71 (38879 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.770-5111C>T		intron_variant	Intron 1 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.770-5111C>T		intron_variant	Intron 1 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107739 AN: 151880 Hom.: 38857 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.709 AC: 107811 AN: 151996 Hom.: 38879 Cov.: 32 AF XY: 0.704 AC XY: 52294 AN XY: 74324

African (AFR) AF: 0.735 AC: 30493 AN: 41470

American (AMR) AF: 0.677 AC: 10344 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2492 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1419 AN: 5144

South Asian (SAS) AF: 0.493 AC: 2373 AN: 4816

European-Finnish (FIN) AF: 0.762 AC: 8033 AN: 10540

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50169 AN: 67960

Other (OTH) AF: 0.720 AC: 1519 AN: 2110

Alfa AF: 0.723 Hom.: 33731

Bravo AF: 0.702

Asia WGS AF: 0.422 AC: 1464 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		0.12
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: rs6889608; hg19: chr5-32719693;