rs17105964

Positions:

• chr11-106698857-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000855.3(GUCY1A2):​c.1991+9655A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 151,942 control chromosomes in the GnomAD database, including 788 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 0.079 (788 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.1991+9655A>G		intron_variant		ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.2084+9655A>G		intron_variant			NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1991+9655A>G		intron_variant		1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.2084+9655A>G		intron_variant		1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.2054+9655A>G		intron_variant		1		ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 11993 AN: 151828 Hom.: 784 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0838

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

GnomAD4 genome AF: 0.0790 AC: 12004 AN: 151942 Hom.: 788 Cov.: 32 AF XY: 0.0794 AC XY: 5897 AN XY: 74266

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0758

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.0289

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0553 Hom.: 47

Bravo AF: 0.0919

Asia WGS AF: 0.0630 AC: 218 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.87

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: rs17105964; hg19: chr11-106569583;