Genetic Variant BBIP1:p.Arg78His (chr10-110900406-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001195305.3(BBIP1):c.233G>A(p.Arg78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,535,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

BBIP1
NM_001195305.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4B:2

Conservation

PhyloP100: 0.805

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022552073).

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.233G>A	p.Arg78His	missense	Exon 4 of 4	NP_001182234.1	A8MTZ0-1
BBIP1	NM_001195306.2		c.233G>A	p.Arg78His	missense	Exon 4 of 4	NP_001182235.1	A8MTZ0-1
BBIP1	NM_001243783.3		c.167G>A	p.Arg56His	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.233G>A	p.Arg78His	missense	Exon 4 of 4	ENSP00000436622.2	A8MTZ0-1
BBIP1	ENST00000605742.5	TSL:1	c.233G>A	p.Arg78His	missense	Exon 4 of 4	ENSP00000474675.1	A8MTZ0-1
BBIP1	ENST00000423273.5	TSL:1	c.158G>A	p.Arg53His	missense	Exon 3 of 3	ENSP00000432274.1	A8MTZ0-3

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000575

AC:

AN:

139116

AF XY:

0.0000530

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000954

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000715

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.0000853

AC:

118

AN:

1383132

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

682516

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31550

American (AMR)

AF:

0.00

AC:

AN:

35646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.0000841

AC:

AN:

35666

South Asian (SAS)

AF:

0.0000632

AC:

AN:

79174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33888

Middle Eastern (MID)

AF:

0.000183

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.0000936

AC:

101

AN:

1078706

Other (OTH)

AF:

0.000121

AC:

AN:

57872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41524

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000540

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Bardet-Biedl syndrome 18 (1)

BBIP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.12

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.70

M_CAP

Benign

0.0056

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.97

PhyloP100

0.81

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.16

Sift

Benign

0.11

Sift4G

Uncertain

0.012

Vest4

0.090

MutPred

0.093

Loss of MoRF binding (P = 0.0082)

MVP

0.055

ClinPred

0.12

GERP RS

2.5

Varity_R

0.12

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over