11-106710471-C-T

Variant names:

• chr11-106710471-C-T
• rs10890568
• NM_000855.3:c.1837-1805G>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.1837-1805G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 144,340 control chromosomes in the GnomAD database, including 19,693 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 0.51 (19693 hom., cov: 25)
• Consequence: GUCY1A2 NM_000855.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 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.1837-1805G>A		intron	N/A	NP_000846.1	P33402-1
	GUCY1A2	NM_001256424.2		c.1930-1805G>A		intron	N/A	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.1837-1805G>A		intron	N/A	ENSP00000431245.2	P33402-1
	GUCY1A2	ENST00000282249.6	TSL:1	c.1930-1805G>A		intron	N/A	ENSP00000282249.2	P33402-2
	GUCY1A2	ENST00000347596.2	TSL:1	c.1900-1805G>A		intron	N/A	ENSP00000344874.2	P33402-3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 73226 AN: 144316 Hom.: 19679 Cov.: 25

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.508 AC: 73253 AN: 144340 Hom.: 19693 Cov.: 25 AF XY: 0.507 AC XY: 35397 AN XY: 69848

African (AFR) AF: 0.685 AC: 26818 AN: 39124

American (AMR) AF: 0.526 AC: 7253 AN: 13778

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1706 AN: 3436

East Asian (EAS) AF: 0.314 AC: 1553 AN: 4952

South Asian (SAS) AF: 0.479 AC: 2254 AN: 4706

European-Finnish (FIN) AF: 0.426 AC: 3705 AN: 8696

Middle Eastern (MID) AF: 0.504 AC: 130 AN: 258

European-Non Finnish (NFE) AF: 0.429 AC: 28590 AN: 66570

Other (OTH) AF: 0.492 AC: 962 AN: 1954

Alfa AF: 0.403 Hom.: 3454

Bravo AF: 0.520

Asia WGS AF: 0.453 AC: 1553 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.69
PhyloP100		-0.14
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: rs10890568; hg19: chr11-106581197;