1-42153706-G-A

Position:

• chr1-42153706-G-A

Variant summary

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

The NM_007102.3(GUCA2B):​c.90+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,176 control chromosomes in the GnomAD database, including 2,330 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 0.17 (2330 hom., cov: 32)
• Consequence: GUCA2B NM_007102.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA2B	NM_007102.3	c.90+166G>A		intron_variant		ENST00000372581.2	NP_009033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA2B	ENST00000372581.2	c.90+166G>A		intron_variant		1	NM_007102.3	ENSP00000361662	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26102 AN: 152058 Hom.: 2329 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.145

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 26123 AN: 152176 Hom.: 2330 Cov.: 32 AF XY: 0.172 AC XY: 12813 AN XY: 74402

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.147

Alfa AF: 0.177 Hom.: 312

Bravo AF: 0.166

Asia WGS AF: 0.264 AC: 918 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	3.8
DANN	Benign	0.85

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: rs2297566; hg19: chr1-42619377;