11-106697184-T-C

Variant summary

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

The NM_000855.3(GUCY1A2):c.1992-9428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,288 control chromosomes in the GnomAD database, including 895 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 0.093 (895 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A2	NM_000855.3	c.1992-9428A>G		intron_variant		ENST00000526355.7
GUCY1A2	NM_001256424.2	c.2085-9428A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1992-9428A>G		intron_variant		1	NM_000855.3	P1
GUCY1A2	ENST00000282249.6	c.2085-9428A>G		intron_variant		1
GUCY1A2	ENST00000347596.2	c.2055-9428A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14181 AN: 152170 Hom.: 894 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0771

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.0961

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

GnomAD4 genome AF: 0.0931 AC: 14184 AN: 152288 Hom.: 895 Cov.: 32 AF XY: 0.0881 AC XY: 6562 AN XY: 74464

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.0771

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.125 Hom.: 659

Bravo AF: 0.0916

Asia WGS AF: 0.0200 AC: 70 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.80

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: rs10502075; hg19: chr11-106567910;