rs143191074
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_152384.3(BBS5):āc.584A>Gā(p.Asp195Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,611,756 control chromosomes in the GnomAD database, including 50 homozygotes. 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: š 0.0018 ( 4 hom., cov: 32)
Exomes š: 0.0013 ( 46 hom. )
Consequence
BBS5
NM_152384.3 missense
NM_152384.3 missense
Scores
1
11
5
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
BBS5 (HGNC:970): (Bardet-Biedl syndrome 5) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011274219).
BP6
?
Variant 2-169493802-A-G is Benign according to our data. Variant chr2-169493802-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 96498.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Likely_benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00183 (279/152352) while in subpopulation AMR AF= 0.0156 (239/15306). AF 95% confidence interval is 0.014. There are 4 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS5 | NM_152384.3 | c.584A>G | p.Asp195Gly | missense_variant | 7/12 | ENST00000295240.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS5 | ENST00000295240.8 | c.584A>G | p.Asp195Gly | missense_variant | 7/12 | 1 | NM_152384.3 | P1 | |
BBS5 | ENST00000392663.6 | c.584A>G | p.Asp195Gly | missense_variant | 7/11 | 1 | |||
BBS5 | ENST00000443151.1 | c.*306A>G | 3_prime_UTR_variant, NMD_transcript_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00183 AC: 279AN: 152234Hom.: 4 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
279
AN:
152234
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00634 AC: 1593AN: 251228Hom.: 34 AF XY: 0.00440 AC XY: 598AN XY: 135806
GnomAD3 exomes
AF:
AC:
1593
AN:
251228
Hom.:
AF XY:
AC XY:
598
AN XY:
135806
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00132 AC: 1933AN: 1459404Hom.: 46 Cov.: 29 AF XY: 0.00104 AC XY: 754AN XY: 726154
GnomAD4 exome
AF:
AC:
1933
AN:
1459404
Hom.:
Cov.:
29
AF XY:
AC XY:
754
AN XY:
726154
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00183 AC: 279AN: 152352Hom.: 4 Cov.: 32 AF XY: 0.00179 AC XY: 133AN XY: 74506
GnomAD4 genome
?
AF:
AC:
279
AN:
152352
Hom.:
Cov.:
32
AF XY:
AC XY:
133
AN XY:
74506
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
3
ExAC
?
AF:
AC:
546
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 16, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 03, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2016 | The D195G variant in the BBS5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D195G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Aspartic Acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D195G as a variant of uncertain significance. - |
Bardet-Biedl syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at