chr6-42173531-G-A

Position:

• chr6-42173531-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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]

GUCA1ANB-GUCA1A (HGNC:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA1A	NM_001384910.1	c.-83G>A		5_prime_UTR_variant	1/4	ENST00000372958.2	NP_001371839.1
GUCA1ANB-GUCA1A	NM_001319061.2	c.-83G>A		5_prime_UTR_variant	3/6		NP_001305990.1
GUCA1ANB-GUCA1A	NM_000409.5	c.-83G>A		5_prime_UTR_variant	3/6		NP_000400.2
GUCA1ANB-GUCA1A	NM_001319062.2	c.-83G>A		5_prime_UTR_variant	2/5		NP_001305991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1A	ENST00000372958.2	c.-83G>A		5_prime_UTR_variant	1/4	1	NM_001384910.1	ENSP00000362049	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25300 AN: 152092 Hom.: 2816 Cov.: 33

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.: 13 AF XY: 0.116 AC XY: 58238 AN XY: 503156

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.: 33 AF XY: 0.163 AC XY: 12103 AN XY: 74416

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

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

Other links and lift over

dbSNP: rs9471793; hg19: chr6-42141269; COSMIC: COSV50003914;