11-106680822-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000855.3(GUCY1A2):c.*6727T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 206,818 control chromosomes in the GnomAD database, including 6,417 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 0.25 (4992 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1425 hom.)
• Consequence: GUCY1A2 NM_000855.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A2	NM_000855.3	c.*6727T>A		3_prime_UTR_variant	8/8	ENST00000526355.7
GUCY1A2	NM_001256424.2	c.*6727T>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.*6727T>A		3_prime_UTR_variant	8/8	1	NM_000855.3	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38350 AN: 151644 Hom.: 4987 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.223 AC: 12256 AN: 55058 Hom.: 1425 Cov.: 0 AF XY: 0.223 AC XY: 5710 AN XY: 25550

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.253 AC: 38379 AN: 151760 Hom.: 4992 Cov.: 31 AF XY: 0.253 AC XY: 18777 AN XY: 74168

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0952

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.241

Alfa AF: 0.101 Hom.: 187

Bravo AF: 0.253

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.2
Dann	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs2000930; hg19: chr11-106551548;