rs75847960

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033028.5(BBS4):c.1451-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,501,516 control chromosomes in the GnomAD database, including 10,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 668 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9425 hom. )

Consequence

BBS4
NM_033028.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.127

Publications

4 publications found

Variant links:

Genes affected

BBS4 (HGNC:969): (Bardet-Biedl syndrome 4) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse. The similar phenotypes exhibited by mutations in BBS gene family members are likely due to the protein's shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene has sequence similarity to O-linked N-acetylglucosamine (O-GlcNAc) transferases in plants and archaebacteria and in human forms a multi-protein "BBSome" complex with seven other BBS proteins. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

BBS4 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
BBS4-related ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 15-72737433-T-C is Benign according to our data. Variant chr15-72737433-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 21732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033028.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS4	NM_033028.5	MANE Select	c.1451-45T>C	intron	N/A	NP_149017.2
BBS4	NM_001320665.2		c.1382-45T>C	intron	N/A	NP_001307594.1	H3BSL2
BBS4	NM_001252678.2		c.935-45T>C	intron	N/A	NP_001239607.1	Q96RK4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS4	ENST00000268057.9	TSL:1 MANE Select	c.1451-45T>C	intron	N/A	ENSP00000268057.4	Q96RK4-1
BBS4	ENST00000395205.7	TSL:1	c.935-45T>C	intron	N/A	ENSP00000378631.3	Q96RK4-3
BBS4	ENST00000566400.6	TSL:1	c.935-45T>C	intron	N/A	ENSP00000456759.2	H3BSL3

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12916

AN:

152142

Hom.:

668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0611

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0820

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0861

GnomAD2 exomes

AF:

0.0813

AC:

16024

AN:

196986

AF XY:

0.0842

show subpopulations

Gnomad AFR exome

AF:

0.0505

Gnomad AMR exome

AF:

0.0488

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.000258

Gnomad FIN exome

AF:

0.0547

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0815

GnomAD4 exome

AF:

0.113

AC:

152567

AN:

1349256

Hom.:

9425

Cov.:

AF XY:

0.112

AC XY:

75334

AN XY:

671982

show subpopulations

African (AFR)

AF:

0.0533

AC:

1662

AN:

31204

American (AMR)

AF:

0.0506

AC:

2011

AN:

39758

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

2632

AN:

24874

East Asian (EAS)

AF:

0.000157

AC:

AN:

38318

South Asian (SAS)

AF:

0.0897

AC:

7148

AN:

79708

European-Finnish (FIN)

AF:

0.0549

AC:

2805

AN:

51088

Middle Eastern (MID)

AF:

0.0902

AC:

502

AN:

5564

European-Non Finnish (NFE)

AF:

0.127

AC:

129733

AN:

1022254

Other (OTH)

AF:

0.107

AC:

6068

AN:

56488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

6821

13642

20463

27284

34105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4600

9200

13800

18400

23000

<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:

0.0849

AC:

12924

AN:

152260

Hom.:

668

Cov.:

AF XY:

0.0810

AC XY:

6027

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0541

AC:

2247

AN:

41556

American (AMR)

AF:

0.0610

AC:

933

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

380

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0810

AC:

391

AN:

4826

European-Finnish (FIN)

AF:

0.0603

AC:

640

AN:

10612

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8026

AN:

68006

Other (OTH)

AF:

0.0852

AC:

180

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

578

1157

1735

2314

2892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0977

Hom.:

126

Bravo

AF:

0.0830

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(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