rs13139571

chr4-155724361-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GUCY1A1	NM_001130682.3	c.1871+2169C>A		intron_variant		ENST00000506455.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A1	ENST00000506455.6	c.1871+2169C>A		intron_variant		1	NM_001130682.3	P1

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

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.240

Alfa AF: 0.241 Hom.: 4530

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs13139571; hg19: chr4-156645513;