Genetic Variant BBIP1:p.Ala73Pro (chr10-110900422-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001195305.3(BBIP1):c.217G>C(p.Ala73Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A73V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

BBIP1
NM_001195305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 18
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBIP1	NM_001195305.3	MANE Select	c.217G>C	p.Ala73Pro	missense	Exon 4 of 4	NP_001182234.1	A8MTZ0-1
BBIP1	NM_001195306.2		c.217G>C	p.Ala73Pro	missense	Exon 4 of 4	NP_001182235.1	A8MTZ0-1
BBIP1	NM_001243783.3		c.151G>C	p.Ala51Pro	missense	Exon 3 of 3	NP_001230712.1	A8MTZ0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBIP1	ENST00000448814.7	TSL:1 MANE Select	c.217G>C	p.Ala73Pro	missense	Exon 4 of 4	ENSP00000436622.2	A8MTZ0-1
BBIP1	ENST00000605742.5	TSL:1	c.217G>C	p.Ala73Pro	missense	Exon 4 of 4	ENSP00000474675.1	A8MTZ0-1
BBIP1	ENST00000423273.5	TSL:1	c.142G>C	p.Ala48Pro	missense	Exon 3 of 3	ENSP00000432274.1	A8MTZ0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1383576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31580

American (AMR)

AF:

0.00

AC:

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35684

South Asian (SAS)

AF:

0.00

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078808

Other (OTH)

AF:

0.00

AC:

AN:

57884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.34

PhyloP100

5.6

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.018

Vest4

0.74

MutPred

0.097

Loss of MoRF binding (P = 0.0564)

MVP

0.16

ClinPred

0.99

GERP RS

4.4

Varity_R

0.99

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over