Variant chr6-42184312-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 NM_002098.6(GUCA1B):c.*503G>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 0.0593 in 204,506 control chromosomes in the GnomAD database, including 469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 344 hom., cov: 32)

Exomes 𝑓: 0.064 ( 125 hom. )

Consequence

GUCA1B
NM_002098.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.39

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=-0.96).

BP6

Variant 6-42184312-C-T is Benign according to our data. Variant chr6-42184312-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 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.*503G>A		3_prime_UTR_variant	4/4	ENST00000230361.4	NP_002089.4	Q9UMX6Q7Z3V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1B	ENST00000230361 linkuse as main transcript	c.*503G>A		3_prime_UTR_variant	4/4	1	NM_002098.6	ENSP00000230361.3		Q9UMX6

Frequencies

GnomAD3 genomes

AF:

0.0575

AC:

8748

AN:

152042

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0896

Gnomad EAS

AF:

0.0686

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0769

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0676

Gnomad OTH

AF:

0.0651

GnomAD4 exome

AF:

0.0645

AC:

3375

AN:

52346

Hom.:

125

AF XY:

0.0608

AC XY:

1648

AN XY:

27086

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.0880

Gnomad4 EAS exome

AF:

0.0568

Gnomad4 SAS exome

AF:

0.0284

Gnomad4 FIN exome

AF:

0.0701

Gnomad4 NFE exome

AF:

0.0688

Gnomad4 OTH exome

AF:

0.0828

GnomAD4 genome

AF:

0.0575

AC:

8752

AN:

152160

Hom.:

344

Cov.:

AF XY:

0.0579

AC XY:

4307

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0896

Gnomad4 EAS

AF:

0.0685

Gnomad4 SAS

AF:

0.0251

Gnomad4 FIN

AF:

0.0769

Gnomad4 NFE

AF:

0.0675

Gnomad4 OTH

AF:

0.0649

Alfa

AF:

0.0316

Hom.:

Bravo

AF:

0.0602

Asia WGS

AF:

0.0580

AC:

201

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 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

2.5

DANN

Benign

0.88

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