rs61736997

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130682.3(GUCY1A1):c.170A>C(p.Glu57Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,613,220 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 405 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 352 hom. )

Consequence

GUCY1A1
NM_001130682.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.96

Publications

8 publications found

Variant links:

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

GUCY1A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014294982).

BP6

Variant 4-155697037-A-C is Benign according to our data. Variant chr4-155697037-A-C is described in ClinVar as Benign. ClinVar VariationId is 1600192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUCY1A1	NM_001130682.3	MANE Select	c.170A>C	p.Glu57Ala	missense	Exon 3 of 10	NP_001124154.1	Q02108-1
GUCY1A1	NM_000856.6		c.170A>C	p.Glu57Ala	missense	Exon 4 of 11	NP_000847.2	Q02108-1
GUCY1A1	NM_001130683.4		c.170A>C	p.Glu57Ala	missense	Exon 3 of 10	NP_001124155.1	Q02108-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUCY1A1	ENST00000506455.6	TSL:1 MANE Select	c.170A>C	p.Glu57Ala	missense	Exon 3 of 10	ENSP00000424361.1	Q02108-1
GUCY1A1	ENST00000296518.11	TSL:1	c.170A>C	p.Glu57Ala	missense	Exon 3 of 10	ENSP00000296518.7	Q02108-1
GUCY1A1	ENST00000511108.5	TSL:1	c.170A>C	p.Glu57Ala	missense	Exon 4 of 11	ENSP00000421493.1	Q02108-1

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5982

AN:

152162

Hom.:

404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.0373

GnomAD2 exomes

AF:

0.0105

AC:

2636

AN:

251136

AF XY:

0.00780

show subpopulations

Gnomad AFR exome

AF:

0.139

Gnomad AMR exome

AF:

0.00843

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00411

AC:

6002

AN:

1460940

Hom.:

352

Cov.:

AF XY:

0.00357

AC XY:

2594

AN XY:

726866

show subpopulations

African (AFR)

AF:

0.140

AC:

4687

AN:

33430

American (AMR)

AF:

0.00929

AC:

415

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000162

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000228

AC:

253

AN:

1111204

Other (OTH)

AF:

0.00952

AC:

575

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

289

578

867

1156

1445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0394

AC:

6000

AN:

152280

Hom.:

405

Cov.:

AF XY:

0.0380

AC XY:

2830

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.135

AC:

5588

AN:

41546

American (AMR)

AF:

0.0175

AC:

268

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000808

AC:

AN:

68028

Other (OTH)

AF:

0.0369

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

256

512

769

1025

1281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0126

Hom.:

291

Bravo

AF:

0.0452

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.135

AC:

593

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0126

AC:

1534

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

GUCY1A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.099

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

PhyloP100

2.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.79

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.024

MPC

0.079

ClinPred

0.0012

GERP RS

1.7

Varity_R

0.038

gMVP

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over