rs145968663

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.1106+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,602,952 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 142 hom. )

Consequence

BBS4
NM_033028.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.220

Publications

0 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=-0.88).

BP6

Variant 15-72735202-T-C is Benign according to our data. Variant chr15-72735202-T-C is described in ClinVar as Benign. ClinVar VariationId is 262134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0681 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.1106+20T>C	intron	N/A	NP_149017.2
BBS4	NM_001320665.2		c.1037+20T>C	intron	N/A	NP_001307594.1	H3BSL2
BBS4	NM_001252678.2		c.590+20T>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.1106+20T>C	intron	N/A	ENSP00000268057.4	Q96RK4-1
BBS4	ENST00000395205.7	TSL:1	c.590+20T>C	intron	N/A	ENSP00000378631.3	Q96RK4-3
BBS4	ENST00000566400.6	TSL:1	c.590+20T>C	intron	N/A	ENSP00000456759.2	H3BSL3

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.0108

AC:

2713

AN:

250872

AF XY:

0.00799

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.0738

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00947

GnomAD4 exome

AF:

0.00236

AC:

3424

AN:

1450640

Hom.:

142

Cov.:

AF XY:

0.00194

AC XY:

1398

AN XY:

722378

show subpopulations

African (AFR)

AF:

0.000932

AC:

AN:

33274

American (AMR)

AF:

0.0702

AC:

3129

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00167

AC:

AN:

39636

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5370

European-Non Finnish (NFE)

AF:

0.0000499

AC:

AN:

1102382

Other (OTH)

AF:

0.00237

AC:

142

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

208

416

624

832

1040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.00479

AC:

729

AN:

152312

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

358

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41568

American (AMR)

AF:

0.0404

AC:

619

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00405

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68018

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00316

Hom.:

Bravo

AF:

0.00863

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome (1)

Bardet-Biedl syndrome 4 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.65

(source)

DANN

Benign

0.59

PhyloP100

-0.22

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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