rs80334351

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.405+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,570,000 control chromosomes in the GnomAD database, including 1,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 104 hom., cov: 32)

Exomes 𝑓: 0.030 ( 986 hom. )

Consequence

BBS4
NM_033028.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.171

Publications

2 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=-0.61).

BP6

Variant 15-72716867-C-T is Benign according to our data. Variant chr15-72716867-C-T is described in ClinVar as Benign. ClinVar VariationId is 262139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0697 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.405+17C>T	intron	N/A	NP_149017.2
BBS4	NM_001320665.2		c.405+17C>T	intron	N/A	NP_001307594.1	H3BSL2
BBS4	NM_001252678.2		c.-117+17C>T	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.405+17C>T	intron	N/A	ENSP00000268057.4	Q96RK4-1
BBS4	ENST00000395205.7	TSL:1	c.-112+17C>T	intron	N/A	ENSP00000378631.3	Q96RK4-3
BBS4	ENST00000566400.6	TSL:1	c.-117+17C>T	intron	N/A	ENSP00000456759.2	H3BSL3

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3909

AN:

152188

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00511

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0733

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.0437

AC:

10459

AN:

239186

AF XY:

0.0406

show subpopulations

Gnomad AFR exome

AF:

0.00568

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0295

Gnomad EAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.0360

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0296

AC:

41897

AN:

1417694

Hom.:

986

Cov.:

AF XY:

0.0295

AC XY:

20874

AN XY:

706524

show subpopulations

African (AFR)

AF:

0.00524

AC:

171

AN:

32626

American (AMR)

AF:

0.135

AC:

5916

AN:

43924

Ashkenazi Jewish (ASJ)

AF:

0.0318

AC:

810

AN:

25448

East Asian (EAS)

AF:

0.000786

AC:

AN:

39452

South Asian (SAS)

AF:

0.0398

AC:

3355

AN:

84346

European-Finnish (FIN)

AF:

0.0367

AC:

1939

AN:

52898

Middle Eastern (MID)

AF:

0.0382

AC:

198

AN:

5188

European-Non Finnish (NFE)

AF:

0.0260

AC:

27929

AN:

1075082

Other (OTH)

AF:

0.0264

AC:

1548

AN:

58730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1719

3438

5157

6876

8595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1062

2124

3186

4248

5310

<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:

0.0256

AC:

3906

AN:

152306

Hom.:

104

Cov.:

AF XY:

0.0271

AC XY:

2020

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00510

AC:

212

AN:

41574

American (AMR)

AF:

0.0733

AC:

1120

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5192

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4818

European-Finnish (FIN)

AF:

0.0340

AC:

361

AN:

10612

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0272

AC:

1848

AN:

68034

Other (OTH)

AF:

0.0284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

197

394

591

788

985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0279

Hom.:

100

Bravo

AF:

0.0292

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Bardet-Biedl syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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