10-110900376-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195305.3(BBIP1):​c.263G>A​(p.Arg88Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,534,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

BBIP1
NM_001195305.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: -3.00
Variant links:
Genes affected
BBIP1 (HGNC:28093): (BBSome interacting protein 1) This gene encodes one of eight proteins that form the BBSome complex and is essential for its assembly. The BBSome complex is involved in trafficking signal receptors to and from the cilia. Mutations in this gene result in Bardet-Biedl syndrome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022710055).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BBIP1NM_001195305.3 linkc.263G>A p.Arg88Gln missense_variant Exon 4 of 4 ENST00000448814.7 NP_001182234.1 A8MTZ0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BBIP1ENST00000448814.7 linkc.263G>A p.Arg88Gln missense_variant Exon 4 of 4 1 NM_001195305.3 ENSP00000436622.2 A8MTZ0-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000431
AC:
6
AN:
139066
Hom.:
0
AF XY:
0.0000265
AC XY:
2
AN XY:
75416
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000411
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000894
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000333
AC:
46
AN:
1382284
Hom.:
0
Cov.:
30
AF XY:
0.0000366
AC XY:
25
AN XY:
682156
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.000140
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000334
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000546
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 18 Uncertain:1
May 02, 2022
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Uncertain:1
Dec 12, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 88 of the BBIP1 protein (p.Arg88Gln). This variant is present in population databases (rs781040735, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with BBIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1044270). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

BBIP1-related disorder Uncertain:1
May 10, 2024
PreventionGenetics, part of Exact Sciences
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

The BBIP1 c.263G>A variant is predicted to result in the amino acid substitution p.Arg88Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0084% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.055
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.024
DANN
Benign
0.89
DEOGEN2
Benign
0.033
T;.;.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.50
.;.;T;T;T
M_CAP
Benign
0.00067
T
MetaRNN
Benign
0.023
T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.18
T
PROVEAN
Benign
-0.12
N;N;N;.;N
REVEL
Benign
0.011
Sift
Benign
0.53
T;T;T;.;T
Sift4G
Benign
0.23
T;T;T;T;T
Vest4
0.061
MutPred
0.17
Loss of MoRF binding (P = 0.001);.;.;Loss of MoRF binding (P = 0.001);.;
MVP
0.014
ClinPred
0.026
T
GERP RS
-5.1
Varity_R
0.016

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781040735; hg19: chr10-112660134; API