chr11-106680822-A-T

Variant names:

• chr11-106680822-A-T
• rs2000930
• NM_000855.3:c.*6727T>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.*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
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 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.*6727T>A		3_prime_UTR	Exon 8 of 8	NP_000846.1
	GUCY1A2	NM_001256424.2		c.*6727T>A		3_prime_UTR	Exon 9 of 9	NP_001243353.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A2	ENST00000526355.7	TSL:1 MANE Select	c.*6727T>A		3_prime_UTR	Exon 8 of 8	ENSP00000431245.2

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

African (AFR) AF: 0.297 AC: 729 AN: 2452

American (AMR) AF: 0.210 AC: 340 AN: 1616

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 653 AN: 3426

East Asian (EAS) AF: 0.127 AC: 1088 AN: 8590

South Asian (SAS) AF: 0.196 AC: 101 AN: 514

European-Finnish (FIN) AF: 0.200 AC: 8 AN: 40

Middle Eastern (MID) AF: 0.246 AC: 88 AN: 358

European-Non Finnish (NFE) AF: 0.244 AC: 8180 AN: 33514

Other (OTH) AF: 0.235 AC: 1069 AN: 4548

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

African (AFR) AF: 0.306 AC: 12682 AN: 41388

American (AMR) AF: 0.224 AC: 3411 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3466

East Asian (EAS) AF: 0.0952 AC: 491 AN: 5158

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2619 AN: 10568

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.246 AC: 16688 AN: 67830

Other (OTH) AF: 0.241 AC: 509 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.23
PhyloP100		1.2
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: rs2000930; hg19: chr11-106551548;