Variant chr6-42184335-C-T 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 ENST00000230361.4(GUCA1B):c.*480G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 220,812 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 165 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 8 hom. )

Consequence

GUCA1B
ENST00000230361.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.00400

Variant links:

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]

GUCA1B 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=-0.91).

BP6

Variant 6-42184335-C-T is Benign according to our data. Variant chr6-42184335-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA1B	NM_002098.6 linkuse as main transcript	c.*480G>A		3_prime_UTR_variant	4/4	ENST00000230361.4	NP_002089.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1B	ENST00000230361.4 linkuse as main transcript	c.*480G>A		3_prime_UTR_variant	4/4	1	NM_002098.6	ENSP00000230361	P1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3884

AN:

152148

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0273

GnomAD4 exome

AF:

0.00516

AC:

354

AN:

68546

Hom.:

AF XY:

0.00495

AC XY:

176

AN XY:

35584

show subpopulations

Gnomad4 AFR exome

AF:

0.0871

Gnomad4 AMR exome

AF:

0.00961

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000655

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000728

Gnomad4 OTH exome

AF:

0.00533

GnomAD4 genome

AF:

0.0256

AC:

3895

AN:

152266

Hom.:

165

Cov.:

AF XY:

0.0245

AC XY:

1827

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0870

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0293

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.91

CADD

Benign

1.5

DANN

Benign

0.83

Splicing

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