1-42153468-A-G

Position:

• chr1-42153468-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007102.3(GUCA2B):​c.18A>G​(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,610,274 control chromosomes in the GnomAD database, including 31,514 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 0.24 (5574 hom., cov: 33)
  • Exomes 𝑓: 0.18 (25940 hom.)
• Consequence: GUCA2B NM_007102.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

Genes affected

GUCA2B (HGNC:4683): (guanylate cyclase activator 2B) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products, including uroguanylin, a member of the guanylin family of peptides and an endogenous ligand of the guanylate cyclase-C receptor. Binding of this peptide to its cognate receptor stimulates an increase in cyclic GMP and may regulate salt and water homeostasis in the intestine and kidneys. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.179 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA2B	NM_007102.3	c.18A>G	p.Ala6Ala	synonymous_variant	1/3	ENST00000372581.2	NP_009033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA2B	ENST00000372581.2	c.18A>G	p.Ala6Ala	synonymous_variant	1/3	1	NM_007102.3	ENSP00000361662.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36976 AN: 152084 Hom.: 5565 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.211 AC: 52531 AN: 248572 Hom.: 6634 AF XY: 0.200 AC XY: 26910 AN XY: 134698

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.382

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.176 AC: 256000 AN: 1458072 Hom.: 25940 Cov.: 30 AF XY: 0.174 AC XY: 126115 AN XY: 725562

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.243 AC: 37024 AN: 152202 Hom.: 5574 Cov.: 33 AF XY: 0.245 AC XY: 18219 AN XY: 74430

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.232

Alfa AF: 0.161 Hom.: 864

Bravo AF: 0.258

Asia WGS AF: 0.300 AC: 1045 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.43

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: rs1047047; hg19: chr1-42619139;