11-106697184-T-C

Variant names:

• chr11-106697184-T-C
• rs10502075
• NM_000855.3:c.1992-9428A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000855.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	NM_000855.3	MANE Select	c.1992-9428A>G		intron	N/A	NP_000846.1	P33402-1
	GUCY1A2	NM_001256424.2		c.2085-9428A>G		intron	N/A	NP_001243353.1	P33402-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	ENST00000526355.7	TSL:1 MANE Select	c.1992-9428A>G		intron	N/A	ENSP00000431245.2	P33402-1
	GUCY1A2	ENST00000282249.6	TSL:1	c.2085-9428A>G		intron	N/A	ENSP00000282249.2	P33402-2
	GUCY1A2	ENST00000347596.2	TSL:1	c.2055-9428A>G		intron	N/A	ENSP00000344874.2	P33402-3

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

African (AFR) AF: 0.0365 AC: 1518 AN: 41564

American (AMR) AF: 0.0734 AC: 1123 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0306 AC: 148 AN: 4832

European-Finnish (FIN) AF: 0.0771 AC: 819 AN: 10616

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9724 AN: 68000

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.126 Hom.: 726

Bravo AF: 0.0916

Asia WGS AF: 0.0200 AC: 70 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10502075; hg19: chr11-106567910;