rs6588923

Variant names:

• chr11-106749166-G-A
• rs6588923
• NM_000855.3:c.1836+27273C>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.1836+27273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 151,936 control chromosomes in the GnomAD database, including 3,794 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 0.19 (3794 hom., cov: 32)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A2	NM_000855.3	c.1836+27273C>T		intron_variant	Intron 6 of 7	ENST00000526355.7	NP_000846.1
GUCY1A2	NM_001256424.2	c.1837-2523C>T		intron_variant	Intron 6 of 8		NP_001243353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A2	ENST00000526355.7	c.1836+27273C>T		intron_variant	Intron 6 of 7	1	NM_000855.3	ENSP00000431245.2
GUCY1A2	ENST00000282249.6	c.1837-2523C>T		intron_variant	Intron 6 of 8	1		ENSP00000282249.2
GUCY1A2	ENST00000347596.2	c.1899+27273C>T		intron_variant	Intron 7 of 8	1		ENSP00000344874.2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28281 AN: 151818 Hom.: 3783 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0903

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.186 AC: 28331 AN: 151936 Hom.: 3794 Cov.: 32 AF XY: 0.182 AC XY: 13499 AN XY: 74276

African (AFR) AF: 0.380 AC: 15724 AN: 41428

American (AMR) AF: 0.143 AC: 2178 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 338 AN: 3468

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5184

South Asian (SAS) AF: 0.0758 AC: 363 AN: 4786

European-Finnish (FIN) AF: 0.0903 AC: 954 AN: 10570

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8104 AN: 67948

Other (OTH) AF: 0.162 AC: 340 AN: 2104

Alfa AF: 0.156 Hom.: 1053

Bravo AF: 0.199

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.36
PhyloP100		-1.0
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: rs6588923; hg19: chr11-106619892;