chr11-106988944-C-T

Variant names:

• chr11-106988944-C-T
• rs17106280
• NM_000855.3:c.304-2813G>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.304-2813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 152,278 control chromosomes in the GnomAD database, including 721 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 0.053 (721 hom., cov: 33)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.304-2813G>A		intron_variant	Intron 1 of 7	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.304-2813G>A		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.304-2813G>A		intron_variant	Intron 1 of 7	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.304-2813G>A		intron_variant	Intron 1 of 8	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.304-2813G>A		intron_variant	Intron 1 of 8	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8041 AN: 152160 Hom.: 718 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0927

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00322

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0529 AC: 8059 AN: 152278 Hom.: 721 Cov.: 33 AF XY: 0.0602 AC XY: 4481 AN XY: 74452

African (AFR) AF: 0.0477 AC: 1982 AN: 41558

American (AMR) AF: 0.194 AC: 2963 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 29 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1557 AN: 5184

South Asian (SAS) AF: 0.0411 AC: 198 AN: 4822

European-Finnish (FIN) AF: 0.0927 AC: 983 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00322 AC: 219 AN: 68024

Other (OTH) AF: 0.0595 AC: 126 AN: 2116

Alfa AF: 0.0321 Hom.: 193

Bravo AF: 0.0635

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.050
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: rs17106280; hg19: chr11-106859670;