5-32711527-C-T

Variant names:

• chr5-32711527-C-T
• rs9716700
• NM_001204375.2:c.-250C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001204375.2(NPR3):​c.-250C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,050,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: NPR3 NM_001204375.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPR3	ENST00000265074.13	c.-250C>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_001204375.2	ENSP00000265074.8

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000190 AC: 2 AN: 1050380 Hom.: 0 Cov.: 20 AF XY: 0.00000202 AC XY: 1 AN XY: 495298

African (AFR) AF: 0.00 AC: 0 AN: 22252

American (AMR) AF: 0.00 AC: 0 AN: 8248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13654

East Asian (EAS) AF: 0.00 AC: 0 AN: 24172

South Asian (SAS) AF: 0.00 AC: 0 AN: 18814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17342

Middle Eastern (MID) AF: 0.000355 AC: 1 AN: 2814

European-Non Finnish (NFE) AF: 0.00000111 AC: 1 AN: 900656

Other (OTH) AF: 0.00 AC: 0 AN: 42428

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		0.69
PromoterAI		0.00080	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9716700; hg19: chr5-32711633;