rs7692387

Variant names:

• chr4-155714157-G-A
• rs7692387
• NM_001130682.3:c.1572+574G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000506455.6(GUCY1A1):​c.1572+574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,104 control chromosomes in the GnomAD database, including 2,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2245 hom., cov: 32)
• Consequence: GUCY1A1 ENST00000506455.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0960
• Publications: 82 publications found

Genes affected

GUCY1A1 (HGNC:4685): (guanylate cyclase 1 soluble subunit alpha 1) 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. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GUCY1A1 Gene-Disease associations (from GenCC):

• Moyamoya disease with early-onset achalasia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-155714157-G-A is Benign according to our data. Variant chr4-155714157-G-A is described in ClinVar as Benign. ClinVar VariationId is 1613866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506455.6. 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
	GUCY1A1	NM_001130682.3	MANE Select	c.1572+574G>A		intron	N/A	NP_001124154.1
	GUCY1A1	NM_000856.6		c.1572+574G>A		intron	N/A	NP_000847.2
	GUCY1A1	NM_001130683.4		c.1572+574G>A		intron	N/A	NP_001124155.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A1	ENST00000506455.6	TSL:1 MANE Select	c.1572+574G>A		intron	N/A	ENSP00000424361.1
	GUCY1A1	ENST00000296518.11	TSL:1	c.1572+574G>A		intron	N/A	ENSP00000296518.7
	GUCY1A1	ENST00000511108.5	TSL:1	c.1572+574G>A		intron	N/A	ENSP00000421493.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24907 AN: 151986 Hom.: 2244 Cov.: 32

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.164 AC: 24914 AN: 152104 Hom.: 2245 Cov.: 32 AF XY: 0.169 AC XY: 12531 AN XY: 74342

African (AFR) AF: 0.0726 AC: 3014 AN: 41522

American (AMR) AF: 0.207 AC: 3158 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5168

South Asian (SAS) AF: 0.176 AC: 847 AN: 4824

European-Finnish (FIN) AF: 0.250 AC: 2633 AN: 10550

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12980 AN: 67976

Other (OTH) AF: 0.171 AC: 360 AN: 2110

Alfa AF: 0.183 Hom.: 8482

Bravo AF: 0.156

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.23
PhyloP100		0.096
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: rs7692387; hg19: chr4-156635309;