rs761760689

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024649.5(BBS1):​c.664G>A​(p.Gly222Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BBS1
NM_024649.5 missense

Scores

9
9
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.85
Variant links:
Genes affected
BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.897

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BBS1NM_024649.5 linkc.664G>A p.Gly222Ser missense_variant Exon 8 of 17 ENST00000318312.12 NP_078925.3 Q8NFJ9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BBS1ENST00000318312.12 linkc.664G>A p.Gly222Ser missense_variant Exon 8 of 17 1 NM_024649.5 ENSP00000317469.7 Q8NFJ9-1
ENSG00000256349ENST00000419755.3 linkc.775G>A p.Gly259Ser missense_variant Exon 8 of 17 2 ENSP00000398526.3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461668
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Pathogenic
0.51
D
BayesDel_noAF
Pathogenic
0.49
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.96
.;D;.;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.90
D;D;D;D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Pathogenic
3.2
.;M;.;M
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-4.3
D;D;D;D
REVEL
Pathogenic
0.89
Sift
Uncertain
0.010
D;D;T;D
Sift4G
Uncertain
0.019
D;D;T;D
Polyphen
1.0
.;D;.;.
Vest4
0.94
MutPred
0.72
.;Loss of sheet (P = 0.0457);.;Loss of sheet (P = 0.0457);
MVP
0.97
MPC
0.66
ClinPred
0.99
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.73
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66287160; API