chr5-32766716-T-C

Variant names:

• chr5-32766716-T-C
• rs3811966
• NM_001204375.2:c.1060-7992T>C

Variant summary

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

The NM_001204375.2(NPR3):​c.1060-7992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,050 control chromosomes in the GnomAD database, including 7,791 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 0.31 (7791 hom., cov: 32)
• Consequence: NPR3 NM_001204375.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPR3	NM_001204375.2	c.1060-7992T>C		intron_variant	Intron 3 of 7	ENST00000265074.13	NP_001191304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.1060-7992T>C		intron_variant	Intron 3 of 7	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46844 AN: 151930 Hom.: 7789 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.308 AC: 46880 AN: 152050 Hom.: 7791 Cov.: 32 AF XY: 0.304 AC XY: 22630 AN XY: 74322

African (AFR) AF: 0.436 AC: 18080 AN: 41444

American (AMR) AF: 0.293 AC: 4486 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 969 AN: 3466

East Asian (EAS) AF: 0.172 AC: 892 AN: 5178

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4824

European-Finnish (FIN) AF: 0.206 AC: 2175 AN: 10580

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17864 AN: 67962

Other (OTH) AF: 0.316 AC: 667 AN: 2108

Alfa AF: 0.304 Hom.: 1481

Bravo AF: 0.316

Asia WGS AF: 0.265 AC: 923 AN: 3478

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	0.57
PhyloP100		-0.057
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: rs3811966; hg19: chr5-32766822;