1-42153468-A-G

Variant names:

• chr1-42153468-A-G
• rs1047047
• NM_007102.3:c.18A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007102.3. 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
	GUCA2B	NM_007102.3	MANE Select	c.18A>G	p.Ala6Ala	synonymous	Exon 1 of 3	NP_009033.1	Q16661

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCA2B	ENST00000372581.2	TSL:1 MANE Select	c.18A>G	p.Ala6Ala	synonymous	Exon 1 of 3	ENSP00000361662.1	Q16661

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

GnomAD2 exomes AF: 0.211 AC: 52531 AN: 248572 AF XY: 0.200

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 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

African (AFR) AF: 0.415 AC: 13878 AN: 33418

American (AMR) AF: 0.307 AC: 13700 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3829 AN: 26130

East Asian (EAS) AF: 0.420 AC: 16685 AN: 39684

South Asian (SAS) AF: 0.173 AC: 14926 AN: 86198

European-Finnish (FIN) AF: 0.163 AC: 8460 AN: 51840

Middle Eastern (MID) AF: 0.182 AC: 1050 AN: 5754

European-Non Finnish (NFE) AF: 0.155 AC: 171837 AN: 1110114

Other (OTH) AF: 0.193 AC: 11635 AN: 60260

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

African (AFR) AF: 0.403 AC: 16714 AN: 41496

American (AMR) AF: 0.284 AC: 4347 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2029 AN: 5170

South Asian (SAS) AF: 0.197 AC: 951 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1795 AN: 10612

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10099 AN: 68020

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.171 Hom.: 1147

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.43
PhyloP100		-0.18
PromoterAI		0.064	Neutral
Mutation Taster		=100/0	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: rs1047047; hg19: chr1-42619139; COSMIC: COSV107472484;