6-42183497-C-T

Variant names:

• chr6-42183497-C-T
• rs1997980
• NM_002098.6:c.*1318G>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.*1318G>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 0.199 in 152,004 control chromosomes in the GnomAD database, including 3,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.20 (3292 hom., cov: 32)
• Consequence: GUCA1B NM_002098.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.0350

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=-0.81).
• BP6: Variant 6-42183497-C-T is Benign according to our data. Variant chr6-42183497-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 356700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCA1B	NM_002098.6	c.*1318G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000230361.4	NP_002089.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCA1B	ENST00000230361	c.*1318G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_002098.6	ENSP00000230361.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30181 AN: 151886 Hom.: 3293 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30190 AN: 152004 Hom.: 3292 Cov.: 32 AF XY: 0.202 AC XY: 14993 AN XY: 74322

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.209

Alfa AF: 0.227 Hom.: 5436

Bravo AF: 0.188

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone dystrophy Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.81
CADD	Benign	3.2
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1997980; hg19: chr6-42151235;