Variant 6-42173588-A-G 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_001384910.1(GUCA1A):c.-26A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,592,506 control chromosomes in the GnomAD database, including 8,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 4430 hom., cov: 33)

Exomes 𝑓: 0.015 ( 3958 hom. )

Consequence

GUCA1A
NM_001384910.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.226

Variant links:

Genes affected

GUCA1A (HGNC:4678): (guanylate cyclase activator 1A) This gene encodes an enzyme that plays a role in the recovery of retinal photoreceptors from photobleaching. This enzyme promotes the activity of retinal guanylyl cyclase-1 (GC1) at low calcium concentrations and inhibits GC1 at high calcium concentrations. Mutations in this gene can cause cone dystrophy 3 and code-rod dystrophy 14. provided by RefSeq, Jul 2020]

GUCA1A links:

GUCA1ANB-GUCA1A (HGNC:):

GUCA1ANB-GUCA1A 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 (BayesDel_noAF=-0.82).

BP6

Variant 6-42173588-A-G is Benign according to our data. Variant chr6-42173588-A-G is described in ClinVar as [Benign]. Clinvar id is 356691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GUCA1A	NM_001384910.1 linkuse as main transcript	c.-26A>G	5_prime_UTR_variant	1/4	ENST00000372958.2
GUCA1ANB-GUCA1A	NM_001319061.2 linkuse as main transcript	c.-26A>G	5_prime_UTR_variant	3/6
GUCA1ANB-GUCA1A	NM_000409.5 linkuse as main transcript	c.-26A>G	5_prime_UTR_variant	3/6
GUCA1ANB-GUCA1A	NM_001319062.2 linkuse as main transcript	c.-26A>G	5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCA1A	ENST00000372958.2 linkuse as main transcript	c.-26A>G		5_prime_UTR_variant	1/4	1	NM_001384910.1	P1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20274

AN:

152134

Hom.:

4410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.00328

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0361

AC:

9069

AN:

250898

Hom.:

1736

AF XY:

0.0269

AC XY:

3646

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.0301

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00299

Gnomad OTH exome

AF:

0.0211

GnomAD4 exome

AF:

0.0151

AC:

21749

AN:

1440254

Hom.:

3958

Cov.:

AF XY:

0.0132

AC XY:

9469

AN XY:

717862

show subpopulations

Gnomad4 AFR exome

AF:

0.470

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.000429

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.0000752

Gnomad4 NFE exome

AF:

0.00192

Gnomad4 OTH exome

AF:

0.0358

GnomAD4 genome

AF:

0.134

AC:

20341

AN:

152252

Hom.:

4430

Cov.:

AF XY:

0.129

AC XY:

9618

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.456

Gnomad4 AMR

AF:

0.0605

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00328

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.0184

Hom.:

655

Bravo

AF:

0.152

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cone dystrophy 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.2

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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