rs4553343

Variant names:

• chr11-106713175-C-A
• rs4553343
• NM_000855.3:c.1837-4509G>T

Variant summary

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

The NM_000855.3(GUCY1A2):​c.1837-4509G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,150 control chromosomes in the GnomAD database, including 1,417 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 0.13 (1417 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	NM_000855.3	MANE Select	c.1837-4509G>T		intron	N/A	NP_000846.1
	GUCY1A2	NM_001256424.2		c.1930-4509G>T		intron	N/A	NP_001243353.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	ENST00000526355.7	TSL:1 MANE Select	c.1837-4509G>T		intron	N/A	ENSP00000431245.2
	GUCY1A2	ENST00000282249.6	TSL:1	c.1930-4509G>T		intron	N/A	ENSP00000282249.2
	GUCY1A2	ENST00000347596.2	TSL:1	c.1900-4509G>T		intron	N/A	ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20028 AN: 152032 Hom.: 1417 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.132 AC: 20031 AN: 152150 Hom.: 1417 Cov.: 32 AF XY: 0.129 AC XY: 9573 AN XY: 74392

African (AFR) AF: 0.170 AC: 7047 AN: 41482

American (AMR) AF: 0.112 AC: 1708 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3468

East Asian (EAS) AF: 0.00637 AC: 33 AN: 5178

South Asian (SAS) AF: 0.126 AC: 609 AN: 4822

European-Finnish (FIN) AF: 0.0656 AC: 696 AN: 10608

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 9002 AN: 67986

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.135 Hom.: 2720

Bravo AF: 0.136

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.40
PhyloP100		-0.26
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: rs4553343; hg19: chr11-106583901;