Variant rs515726134 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_001195305.3(BBIP1):c.173T>G(p.Leu58Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,535,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L58L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

BBIP1
NM_001195305.3 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 8.67

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]

BBIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.38 CDS is truncated, and there are 2 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 10-110900466-A-C is Pathogenic according to our data. Variant chr10-110900466-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 126379.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-110900466-A-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBIP1	NM_001195305.3 linkuse as main transcript	c.173T>G	p.Leu58Ter	stop_gained	4/4	ENST00000448814.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBIP1	ENST00000448814.7 linkuse as main transcript	c.173T>G	p.Leu58Ter	stop_gained	4/4	1	NM_001195305.3		A8MTZ0-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00000715

AC:

AN:

139808

Hom.:

AF XY:

0.0000132

AC XY:

AN XY:

75690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1383572

Hom.:

Cov.:

AF XY:

0.00000879

AC XY:

AN XY:

682736

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:

0.0000130

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.0000688

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 18

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2014

- -

Bardet-Biedl syndrome 1

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

MutationTaster

Benign

1.0

D;D;D;D;D

Vest4

0.25

GERP RS

5.3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over