NM_001130682.3:c.255+7G>T

Variant names:

• chr4-155697129-G-T
• rs1009102178
• NM_001130682.3:c.255+7G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001130682.3(GUCY1A1):​c.255+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,604,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: GUCY1A1 NM_001130682.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001734
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.267
• Publications: 0 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: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-155697129-G-T is Benign according to our data. Variant chr4-155697129-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3604296.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130682.3. 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
	GUCY1A1	NM_001130682.3	MANE Select	c.255+7G>T		splice_region intron	N/A	NP_001124154.1	Q02108-1
	GUCY1A1	NM_000856.6		c.255+7G>T		splice_region intron	N/A	NP_000847.2	Q02108-1
	GUCY1A1	NM_001130683.4		c.255+7G>T		splice_region intron	N/A	NP_001124155.1	Q02108-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1A1	ENST00000506455.6	TSL:1 MANE Select	c.255+7G>T		splice_region intron	N/A	ENSP00000424361.1	Q02108-1
	GUCY1A1	ENST00000296518.11	TSL:1	c.255+7G>T		splice_region intron	N/A	ENSP00000296518.7	Q02108-1
	GUCY1A1	ENST00000511108.5	TSL:1	c.255+7G>T		splice_region intron	N/A	ENSP00000421493.1	Q02108-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248356 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000392 AC: 57 AN: 1452602 Hom.: 0 Cov.: 29 AF XY: 0.0000346 AC XY: 25 AN XY: 722198

African (AFR) AF: 0.00 AC: 0 AN: 33144

American (AMR) AF: 0.00 AC: 0 AN: 44152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.0000516 AC: 57 AN: 1105232

Other (OTH) AF: 0.00 AC: 0 AN: 59990

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely 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	-0.71
CADD	Benign	5.2
DANN	Benign	0.77
PhyloP100		-0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.012
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: rs1009102178; hg19: chr4-156618281;