Variant chr4-155696940-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130682.3(GUCY1A1):c.73G>A(p.Val25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,613,388 control chromosomes in the GnomAD database, including 433 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.030 ( 230 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 203 hom. )

Consequence

GUCY1A1
NM_001130682.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.77

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015866458).

BP6

Variant 4-155696940-G-A is Benign according to our data. Variant chr4-155696940-G-A is described in ClinVar as [Benign]. Clinvar id is 715600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY1A1	NM_001130682.3 linkuse as main transcript	c.73G>A	p.Val25Ile	missense_variant	3/10	ENST00000506455.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY1A1	ENST00000506455.6 linkuse as main transcript	c.73G>A	p.Val25Ile	missense_variant	3/10	1	NM_001130682.3	P1	Q02108-1

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4505

AN:

152130

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.00782

AC:

1961

AN:

250876

Hom.:

AF XY:

0.00589

AC XY:

798

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00632

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00304

AC:

4449

AN:

1461140

Hom.:

203

Cov.:

AF XY:

0.00269

AC XY:

1952

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.00692

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.0297

AC:

4529

AN:

152248

Hom.:

230

Cov.:

AF XY:

0.0290

AC XY:

2160

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.0332

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0944

AC:

416

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00921

AC:

1118

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.042

T;T;T;.;T;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.66

.;T;.;T;.;.;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.020

N;.;N;N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.34

T;.;T;T;T;T;T

Sift4G

Benign

0.48

T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;B;B;B

Vest4

0.015

MVP

0.78

MPC

0.062

ClinPred

0.010

GERP RS

5.9

Varity_R

0.057

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over