11-107000380-T-G

Variant names:

• chr11-107000380-T-G
• rs10502081
• NM_000855.3:c.304-14249A>C

Variant summary

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

The NM_000855.3(GUCY1A2):​c.304-14249A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 152,164 control chromosomes in the GnomAD database, including 773 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 0.069 (773 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.304-14249A>C		intron_variant	Intron 1 of 7	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.304-14249A>C		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.304-14249A>C		intron_variant	Intron 1 of 7	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.304-14249A>C		intron_variant	Intron 1 of 8	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.304-14249A>C		intron_variant	Intron 1 of 8	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10483 AN: 152044 Hom.: 767 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.00508

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0692 AC: 10527 AN: 152164 Hom.: 773 Cov.: 32 AF XY: 0.0674 AC XY: 5012 AN XY: 74408

African (AFR) AF: 0.190 AC: 7892 AN: 41504

American (AMR) AF: 0.0421 AC: 643 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3468

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5154

South Asian (SAS) AF: 0.0461 AC: 222 AN: 4820

European-Finnish (FIN) AF: 0.00508 AC: 54 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0196 AC: 1332 AN: 68004

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0281 Hom.: 249

Bravo AF: 0.0779

Asia WGS AF: 0.0330 AC: 115 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		0.41
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: rs10502081; hg19: chr11-106871106;