11-106987949-T-C

Variant names:

• chr11-106987949-T-C
• rs11211996
• NM_000855.3:c.304-1818A>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.304-1818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,080 control chromosomes in the GnomAD database, including 2,320 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 0.15 (2320 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.304-1818A>G		intron_variant	Intron 1 of 7	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.304-1818A>G		intron_variant	Intron 1 of 8		NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.304-1818A>G		intron_variant	Intron 1 of 7	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.304-1818A>G		intron_variant	Intron 1 of 8	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.304-1818A>G		intron_variant	Intron 1 of 8	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22130 AN: 151962 Hom.: 2320 Cov.: 32

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.145 AC: 22125 AN: 152080 Hom.: 2320 Cov.: 32 AF XY: 0.141 AC XY: 10473 AN XY: 74342

African (AFR) AF: 0.0375 AC: 1555 AN: 41510

American (AMR) AF: 0.104 AC: 1583 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5160

South Asian (SAS) AF: 0.0437 AC: 211 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2356 AN: 10536

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15031 AN: 67974

Other (OTH) AF: 0.129 AC: 272 AN: 2108

Alfa AF: 0.180 Hom.: 1479

Bravo AF: 0.132

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		-0.11
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: rs11211996; hg19: chr11-106858675;