6-42184327-G-A

Variant summary

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

The NM_002098.6(GUCA1B):c.*488C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 214,826 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (7 hom.)
• Consequence: GUCA1B NM_002098.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.32

Genes affected

GUCA1B (HGNC:4679): (guanylate cyclase activator 1B) The protein encoded by this gene is a calcium-binding protein that activates photoreceptor guanylate cyclases. This gene may have arisen due to a gene duplication event since there is a highly similar gene clustered with it on chromosome 6. Mutations in this gene can cause a form of retinitis pigmentosa. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-42184327-G-A is Benign according to our data. Variant chr6-42184327-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 356719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCA1B	NM_002098.6	c.*488C>T		3_prime_UTR_variant	4/4	ENST00000230361.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCA1B	ENST00000230361.4	c.*488C>T		3_prime_UTR_variant	4/4	1	NM_002098.6	P1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2947 AN: 152014 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0173

GnomAD4 exome AF: 0.00429 AC: 269 AN: 62696 Hom.: 7 AF XY: 0.00412 AC XY: 134 AN XY: 32560

Gnomad4 AFR exome AF: 0.0629

Gnomad4 AMR exome AF: 0.00805

Gnomad4 ASJ exome AF: 0.00217

Gnomad4 EAS exome AF: 0.000519

Gnomad4 SAS exome AF: 0.000493

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000904

Gnomad4 OTH exome AF: 0.00643

GnomAD4 genome AF: 0.0194 AC: 2958 AN: 152130 Hom.: 81 Cov.: 32 AF XY: 0.0190 AC XY: 1415 AN XY: 74370

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.000777

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0128 Hom.: 12

Bravo AF: 0.0224

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cone dystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa 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	-0.90
Cadd	Benign	3.5
Dann	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7764586; hg19: chr6-42152065;