rs10890590

Positions:

• chr11-106795333-G-A

Variant summary

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

The NM_000855.3(GUCY1A2):​c.1692+14660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,028 control chromosomes in the GnomAD database, including 5,601 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 0.26 (5601 hom., cov: 33)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

GUCY1A2 (HGNC:4684): (guanylate cyclase 1 soluble subunit alpha 2) Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A2	NM_000855.3	c.1692+14660C>T		intron_variant		ENST00000526355.7
GUCY1A2	NM_001256424.2	c.1692+14660C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1692+14660C>T		intron_variant		1	NM_000855.3	P1
GUCY1A2	ENST00000282249.6	c.1692+14660C>T		intron_variant		1
GUCY1A2	ENST00000347596.2	c.1755+14660C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40119 AN: 151910 Hom.: 5595 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.264 AC: 40148 AN: 152028 Hom.: 5601 Cov.: 33 AF XY: 0.269 AC XY: 19994 AN XY: 74308

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.243

Alfa AF: 0.262 Hom.: 3037

Bravo AF: 0.260

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.45

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: rs10890590; hg19: chr11-106666059;