11-106939832-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000855.3(GUCY1A2):c.834T>C(p.Ser278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,832 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (102 hom.)
• Consequence: GUCY1A2 NM_000855.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-106939832-A-G is Benign according to our data. Variant chr11-106939832-A-G is described in ClinVar as [Benign]. Clinvar id is 770221.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.719 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A2	NM_000855.3	c.834T>C	p.Ser278=	synonymous_variant	4/8	ENST00000526355.7
GUCY1A2	NM_001256424.2	c.834T>C	p.Ser278=	synonymous_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.834T>C	p.Ser278=	synonymous_variant	4/8	1	NM_000855.3	P1
GUCY1A2	ENST00000282249.6	c.834T>C	p.Ser278=	synonymous_variant	4/9	1
GUCY1A2	ENST00000347596.2	c.834T>C	p.Ser278=	synonymous_variant	4/9	1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152204 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00935 AC: 2351 AN: 251404 Hom.: 81 AF XY: 0.00671 AC XY: 912 AN XY: 135878

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.0645

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00337

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00222 AC: 3245 AN: 1461510 Hom.: 102 Cov.: 31 AF XY: 0.00185 AC XY: 1344 AN XY: 727074

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.0593

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00307 AC: 468 AN: 152322 Hom.: 15 Cov.: 32 AF XY: 0.00320 AC XY: 238 AN XY: 74484

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.0257

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.00550

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.12
Dann	Benign	0.49

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: rs117646729; hg19: chr11-106810558;