Variant 6-42173531-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001384910.1(GUCA1A):c.-83G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,122,758 control chromosomes in the GnomAD database, including 10,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2819 hom., cov: 33)

Exomes 𝑓: 0.12 ( 7571 hom. )

Consequence

GUCA1A
NM_001384910.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-42173531-G-A is Benign according to our data. Variant chr6-42173531-G-A is described in ClinVar as [Benign]. Clinvar id is 356690.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GUCA1A	NM_001384910.1 linkuse as main transcript	c.-83G>A	5_prime_UTR_variant	1/4	ENST00000372958.2
GUCA1ANB-GUCA1A	NM_001319061.2 linkuse as main transcript	c.-83G>A	5_prime_UTR_variant	3/6
GUCA1ANB-GUCA1A	NM_000409.5 linkuse as main transcript	c.-83G>A	5_prime_UTR_variant	3/6
GUCA1ANB-GUCA1A	NM_001319062.2 linkuse as main transcript	c.-83G>A	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.-83G>A		5_prime_UTR_variant	1/4	1	NM_001384910.1	P1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25300

AN:

152092

Hom.:

2816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0862

Gnomad FIN

AF:

0.0857

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.116

AC:

112801

AN:

970548

Hom.:

7571

Cov.:

AF XY:

0.116

AC XY:

58238

AN XY:

503156

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.0701

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.00260

Gnomad4 SAS exome

AF:

0.0875

Gnomad4 FIN exome

AF:

0.0847

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.166

AC:

25320

AN:

152210

Hom.:

2819

Cov.:

AF XY:

0.163

AC XY:

12103

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.0860

Gnomad4 FIN

AF:

0.0857

Gnomad4 NFE

AF:

0.123

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.133

Hom.:

514

Bravo

AF:

0.173

Asia WGS

AF:

0.0580

AC:

204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cone dystrophy 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.94

DANN

Benign

0.49

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