11-106939832-A-G

Variant names:

• chr11-106939832-A-G
• rs117646729
• NM_000855.3:c.834T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000855.3(GUCY1A2):​c.834T>C​(p.Ser278Ser) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.719
• Publications: 2 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 -21 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 VariationId is 770221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	NM_000855.3	MANE Select	c.834T>C	p.Ser278Ser	synonymous	Exon 4 of 8	NP_000846.1	P33402-1
	GUCY1A2	NM_001256424.2		c.834T>C	p.Ser278Ser	synonymous	Exon 4 of 9	NP_001243353.1	P33402-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	ENST00000526355.7	TSL:1 MANE Select	c.834T>C	p.Ser278Ser	synonymous	Exon 4 of 8	ENSP00000431245.2	P33402-1
	GUCY1A2	ENST00000282249.6	TSL:1	c.834T>C	p.Ser278Ser	synonymous	Exon 4 of 9	ENSP00000282249.2	P33402-2
	GUCY1A2	ENST00000347596.2	TSL:1	c.834T>C	p.Ser278Ser	synonymous	Exon 4 of 9	ENSP00000344874.2	P33402-3

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

GnomAD2 exomes AF: 0.00935 AC: 2351 AN: 251404 AF XY: 0.00671

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 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

African (AFR) AF: 0.000627 AC: 21 AN: 33470

American (AMR) AF: 0.0593 AC: 2654 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0111 AC: 439 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111688

Other (OTH) AF: 0.00171 AC: 103 AN: 60378

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

African (AFR) AF: 0.00115 AC: 48 AN: 41582

American (AMR) AF: 0.0257 AC: 393 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.00550

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.49
PhyloP100		-0.72
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: rs117646729; hg19: chr11-106810558;