rs13306004

Variant names:

• chr1-153679032-G-A
• rs13306004
• NM_000906.4:c.-77G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000906.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR1	NM_000906.4	MANE Select	c.-77G>A		5_prime_UTR	Exon 1 of 22	NP_000897.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPR1	ENST00000368680.4	TSL:1 MANE Select	c.-77G>A		5_prime_UTR	Exon 1 of 22	ENSP00000357669.3	P16066
	NPR1	ENST00000955927.1		c.-77G>A		5_prime_UTR	Exon 1 of 23	ENSP00000625986.1
	NPR1	ENST00000932961.1		c.-77G>A		5_prime_UTR	Exon 1 of 23	ENSP00000603020.1

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

African (AFR) AF: 0.0519 AC: 1215 AN: 23418

American (AMR) AF: 0.0179 AC: 197 AN: 11026

Ashkenazi Jewish (ASJ) AF: 0.000355 AC: 6 AN: 16882

East Asian (EAS) AF: 0.0133 AC: 373 AN: 28056

South Asian (SAS) AF: 0.0511 AC: 2787 AN: 54498

European-Finnish (FIN) AF: 0.0000339 AC: 1 AN: 29498

Middle Eastern (MID) AF: 0.00703 AC: 24 AN: 3412

European-Non Finnish (NFE) AF: 0.000280 AC: 280 AN: 999404

Other (OTH) AF: 0.00956 AC: 480 AN: 50206

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

African (AFR) AF: 0.0525 AC: 2184 AN: 41566

American (AMR) AF: 0.0120 AC: 183 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0136 AC: 70 AN: 5158

South Asian (SAS) AF: 0.0507 AC: 245 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68000

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.1
DANN	Benign	0.92
PhyloP100		0.059
PromoterAI		-0.0078	Neutral
Mutation Taster		=299/1	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: rs13306004; hg19: chr1-153651508;