Variant rs760064445 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000454061.5(BBIP1):c.191C>T(p.Ala64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 680,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 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. A64G) has been classified as Likely benign.

Frequency

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

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

BBIP1
ENST00000454061.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.124

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:

(HGNC:):

links:

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=0.062074542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBIP1	NM_001195305.3 linkuse as main transcript	c.38-6071C>T		intron_variant		ENST00000448814.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBIP1	ENST00000448814.7 linkuse as main transcript	c.38-6071C>T		intron_variant		1	NM_001195305.3		A8MTZ0-1
	ENST00000619110.1 linkuse as main transcript	n.201G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000176

AC:

AN:

113646

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

62098

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000539

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:

0.0000214

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

528850

Hom.:

Cov.:

AF XY:

0.0000384

AC XY:

AN XY:

286768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000343

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:

0.0000355

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

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

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BBIP1-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 23, 2023

The BBIP1 c.191C>T variant is predicted to result in the amino acid substitution p.Ala64Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0052% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-112667441-G-A). 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

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.4

DANN

Benign

0.92

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0049

M_CAP

Benign

0.0012

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.013

Vest4

0.12

MutPred

0.27

Gain of sheet (P = 0.0166);

MVP

0.014

ClinPred

0.13

GERP RS

-0.077

gMVP

0.0031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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