rs13306004

Positions:

• chr1-153679032-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000906.4(NPR1):​c.-77G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 1,368,670 control chromosomes in the GnomAD database, including 232 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 0.018 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (164 hom.)
• Consequence: NPR1 NM_000906.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

Genes affected

NPR1 (HGNC:7943): (natriuretic peptide receptor 1) Guanylyl cyclases, catalyzing the production of cGMP from GTP, are classified as soluble and membrane forms (Garbers and Lowe, 1994 [PubMed 7982997]). The membrane guanylyl cyclases, often termed guanylyl cyclases A through F, form a family of cell-surface receptors with a similar topographic structure: an extracellular ligand-binding domain, a single membrane-spanning domain, and an intracellular region that contains a protein kinase-like domain and a cyclase catalytic domain. GC-A and GC-B function as receptors for natriuretic peptides; they are also referred to as atrial natriuretic peptide receptor A (NPR1) and type B (NPR2; MIM 108961). Also see NPR3 (MIM 108962), which encodes a protein with only the ligand-binding transmembrane and 37-amino acid cytoplasmic domains. NPR1 is a membrane-bound guanylate cyclase that serves as the receptor for both atrial and brain natriuretic peptides (ANP (MIM 108780) and BNP (MIM 600295), respectively).[supplied by OMIM, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR1	NM_000906.4	c.-77G>A		5_prime_UTR_variant	1/22	ENST00000368680.4
NPR1	XM_005245218.3	c.-77G>A		5_prime_UTR_variant	1/21
NPR1	XM_017001374.3	c.-77G>A		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR1	ENST00000368680.4	c.-77G>A		5_prime_UTR_variant	1/22	1	NM_000906.4	P1

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2716 AN: 152154 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00441 AC: 5363 AN: 1216400 Hom.: 164 Cov.: 29 AF XY: 0.00534 AC XY: 3140 AN XY: 588562

Gnomad4 AFR exome AF: 0.0519

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.000355

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.0511

Gnomad4 FIN exome AF: 0.0000339

Gnomad4 NFE exome AF: 0.000280

Gnomad4 OTH exome AF: 0.00956

GnomAD4 genome AF: 0.0179 AC: 2732 AN: 152270 Hom.: 68 Cov.: 32 AF XY: 0.0178 AC XY: 1322 AN XY: 74462

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0136

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00971 Hom.: 1

Bravo AF: 0.0196

Asia WGS AF: 0.0470 AC: 167 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.92

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

Other links and lift over

dbSNP: rs13306004; hg19: chr1-153651508;