rs17106280

Positions:

• chr11-106988944-C-T

Variant summary

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

The NM_000855.3(GUCY1A2):​c.304-2813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 152,278 control chromosomes in the GnomAD database, including 721 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 0.053 (721 hom., cov: 33)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A2	NM_000855.3	c.304-2813G>A		intron_variant		ENST00000526355.7
GUCY1A2	NM_001256424.2	c.304-2813G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.304-2813G>A		intron_variant		1	NM_000855.3	P1
GUCY1A2	ENST00000282249.6	c.304-2813G>A		intron_variant		1
GUCY1A2	ENST00000347596.2	c.304-2813G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8041 AN: 152160 Hom.: 718 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0927

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00322

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0529 AC: 8059 AN: 152278 Hom.: 721 Cov.: 33 AF XY: 0.0602 AC XY: 4481 AN XY: 74452

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.0411

Gnomad4 FIN AF: 0.0927

Gnomad4 NFE AF: 0.00322

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.0364 Hom.: 138

Bravo AF: 0.0635

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.73

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: rs17106280; hg19: chr11-106859670;