chr1-153685711-A-T

Position:

• chr1-153685711-A-T

Variant summary

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

The NM_000906.4(NPR1):​c.1606-95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 922,988 control chromosomes in the GnomAD database, including 4,217 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 0.11 (1284 hom., cov: 31)
  • Exomes 𝑓: 0.076 (2933 hom.)
• Consequence: NPR1 NM_000906.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPR1	NM_000906.4	c.1606-95A>T		intron_variant		ENST00000368680.4	NP_000897.3
NPR1	XM_005245218.3	c.1606-95A>T		intron_variant			XP_005245275.1
NPR1	XM_017001374.3	c.1606-95A>T		intron_variant			XP_016856863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPR1	ENST00000368680.4	c.1606-95A>T		intron_variant		1	NM_000906.4	ENSP00000357669	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16794 AN: 151950 Hom.: 1270 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.0765 AC: 58969 AN: 770922 Hom.: 2933 AF XY: 0.0774 AC XY: 31470 AN XY: 406610

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.0590

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.000165

Gnomad4 SAS exome AF: 0.0972

Gnomad4 FIN exome AF: 0.0606

Gnomad4 NFE exome AF: 0.0724

Gnomad4 OTH exome AF: 0.0893

GnomAD4 genome AF: 0.111 AC: 16834 AN: 152066 Hom.: 1284 Cov.: 31 AF XY: 0.109 AC XY: 8103 AN XY: 74350

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0918

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0705

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0935 Hom.: 118

Bravo AF: 0.117

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.65

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: rs3891075; hg19: chr1-153658187;