rs34839859
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_019098.5(CNGB3):c.1356G>A(p.Gln452Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00965 in 1,613,948 control chromosomes in the GnomAD database, including 1,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.051 ( 677 hom., cov: 32)
Exomes 𝑓: 0.0053 ( 595 hom. )
Consequence
CNGB3
NM_019098.5 synonymous
NM_019098.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.09
Genes affected
CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 8-86629043-C-T is Benign according to our data. Variant chr8-86629043-C-T is described in ClinVar as [Benign]. Clinvar id is 261082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-86629043-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.09 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNGB3 | NM_019098.5 | c.1356G>A | p.Gln452Gln | synonymous_variant | 12/18 | ENST00000320005.6 | NP_061971.3 | |
CNGB3 | XM_011517138.3 | c.942G>A | p.Gln314Gln | synonymous_variant | 10/16 | XP_011515440.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNGB3 | ENST00000320005.6 | c.1356G>A | p.Gln452Gln | synonymous_variant | 12/18 | 1 | NM_019098.5 | ENSP00000316605.5 | ||
CNGB3 | ENST00000681546.1 | n.1176G>A | non_coding_transcript_exon_variant | 7/13 | ||||||
CNGB3 | ENST00000681746.1 | n.1356G>A | non_coding_transcript_exon_variant | 12/19 | ENSP00000505959.1 |
Frequencies
GnomAD3 genomes AF: 0.0514 AC: 7810AN: 152076Hom.: 675 Cov.: 32
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GnomAD3 exomes AF: 0.0139 AC: 3492AN: 250978Hom.: 269 AF XY: 0.0103 AC XY: 1397AN XY: 135606
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GnomAD4 exome AF: 0.00529 AC: 7738AN: 1461752Hom.: 595 Cov.: 32 AF XY: 0.00454 AC XY: 3301AN XY: 727180
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GnomAD4 genome AF: 0.0515 AC: 7837AN: 152196Hom.: 677 Cov.: 32 AF XY: 0.0489 AC XY: 3643AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Achromatopsia Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 02, 2019 | - - |
Severe early-childhood-onset retinal dystrophy 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. - |
Achromatopsia 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at