rs13139571

Variant names:

• chr4-155724361-C-A
• rs13139571
• NM_001130682.3:c.1871+2169C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130682.3(GUCY1A1):​c.1871+2169C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,056 control chromosomes in the GnomAD database, including 3,788 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 0.22 (3788 hom., cov: 32)
• Consequence: GUCY1A1 NM_001130682.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 68 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

LOC105377506 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1A1	NM_001130682.3	c.1871+2169C>A		intron_variant	Intron 9 of 9	ENST00000506455.6	NP_001124154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1A1	ENST00000506455.6	c.1871+2169C>A		intron_variant	Intron 9 of 9	1	NM_001130682.3	ENSP00000424361.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33629 AN: 151938 Hom.: 3780 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.221 AC: 33655 AN: 152056 Hom.: 3788 Cov.: 32 AF XY: 0.223 AC XY: 16589 AN XY: 74320

African (AFR) AF: 0.157 AC: 6535 AN: 41506

American (AMR) AF: 0.257 AC: 3913 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 830 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1101 AN: 5148

South Asian (SAS) AF: 0.239 AC: 1148 AN: 4812

European-Finnish (FIN) AF: 0.245 AC: 2596 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16534 AN: 67972

Other (OTH) AF: 0.240 AC: 507 AN: 2114

Alfa AF: 0.235 Hom.: 13072

Bravo AF: 0.218

Asia WGS AF: 0.237 AC: 823 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.017
DANN	Benign	0.16
PhyloP100		-1.9
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: rs13139571; hg19: chr4-156645513;