rs35487251
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2
The NM_152384.3(BBS5):c.620G>A(p.Arg207His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,576,430 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207C) has been classified as Uncertain significance.
Frequency
Consequence
NM_152384.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS5 | NM_152384.3 | c.620G>A | p.Arg207His | missense_variant, splice_region_variant | 8/12 | ENST00000295240.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS5 | ENST00000295240.8 | c.620G>A | p.Arg207His | missense_variant, splice_region_variant | 8/12 | 1 | NM_152384.3 | P1 | |
BBS5 | ENST00000392663.6 | c.619-1858G>A | intron_variant | 1 | |||||
BBS5 | ENST00000443151.1 | c.*342G>A | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00612 AC: 931AN: 152006Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00656 AC: 1643AN: 250580Hom.: 11 AF XY: 0.00681 AC XY: 923AN XY: 135514
GnomAD4 exome AF: 0.00803 AC: 11437AN: 1424306Hom.: 86 Cov.: 26 AF XY: 0.00798 AC XY: 5667AN XY: 710514
GnomAD4 genome ? AF: 0.00612 AC: 931AN: 152124Hom.: 1 Cov.: 32 AF XY: 0.00617 AC XY: 459AN XY: 74374
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 25, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 18, 2022 | Variant summary: BBS5 c.620G>A (p.Arg207His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0066 in 250580 control chromosomes in the gnomAD database, including 11 homozygotes. The observed variant frequency is approximately 10 fold of the estimated maximal expected allele frequency for a pathogenic variant in BBS5 causing Bardet-Biedl Syndrome phenotype (0.00062), strongly suggesting that the variant is benign. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | BBS5: BP4, BS2 - |
Bardet-Biedl syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at