4-122743149-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_152618.3(BBS12):c.1257C>T(p.Ser419Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
BBS12
NM_152618.3 synonymous
NM_152618.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.293
Genes affected
BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 4-122743149-C-T is Benign according to our data. Variant chr4-122743149-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 220044.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BP7
Synonymous conserved (PhyloP=0.293 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| BBS12 | NM_152618.3 | c.1257C>T | p.Ser419Ser | synonymous_variant | 2/2 | ENST00000314218.8 | NP_689831.2 | |
| BBS12 | NM_001178007.2 | c.1257C>T | p.Ser419Ser | synonymous_variant | 3/3 | NP_001171478.1 | ||
| BBS12 | XM_011531680.3 | c.1257C>T | p.Ser419Ser | synonymous_variant | 2/2 | XP_011529982.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.000237 AC: 36AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000362 AC: 91AN: 251462Hom.: 0 AF XY: 0.000405 AC XY: 55AN XY: 135908
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GnomAD4 exome AF: 0.000173 AC: 253AN: 1461888Hom.: 0 Cov.: 72 AF XY: 0.000194 AC XY: 141AN XY: 727244
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GnomAD4 genome 0.000237 AC: 36AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74342
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome 12 Uncertain:1Benign:1
| Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 06, 2020 | - - |
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
BBS12-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 23, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Bardet-Biedl syndrome Benign:1
| Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
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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