11-106818892-C-T

Variant names:

• chr11-106818892-C-T
• rs11211933
• NM_000855.3:c.1207-8414G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000855.3(GUCY1A2):​c.1207-8414G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,074 control chromosomes in the GnomAD database, including 2,448 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 0.17 (2448 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.1207-8414G>A		intron_variant	Intron 4 of 7	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.1207-8414G>A		intron_variant	Intron 4 of 8		NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1207-8414G>A		intron_variant	Intron 4 of 7	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.1207-8414G>A		intron_variant	Intron 4 of 8	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.1270-8414G>A		intron_variant	Intron 5 of 8	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25240 AN: 151956 Hom.: 2450 Cov.: 32

Gnomad AFR AF: 0.0687

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.166 AC: 25231 AN: 152074 Hom.: 2448 Cov.: 32 AF XY: 0.165 AC XY: 12287 AN XY: 74338

African (AFR) AF: 0.0687 AC: 2853 AN: 41504

American (AMR) AF: 0.146 AC: 2219 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1446 AN: 5164

South Asian (SAS) AF: 0.245 AC: 1183 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1918 AN: 10574

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13978 AN: 67974

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.174 Hom.: 359

Bravo AF: 0.161

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.66
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: rs11211933; hg19: chr11-106689618;