rs114672242

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_033028.5(BBS4):c.865-22G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,614,170 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0042 ( 6 hom., cov: 29)

Exomes 𝑓: 0.00041 ( 4 hom. )

Consequence

BBS4
NM_033028.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.39

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), 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

new If you want to explore the variant's impact on the transcript NM_033028.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 15-72731533-G-C is Benign according to our data. Variant chr15-72731533-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 262144.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

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.865-22G>C	intron	N/A	NP_149017.2
BBS4	NM_001320665.2		c.796-22G>C	intron	N/A	NP_001307594.1	H3BSL2
BBS4	NM_001252678.2		c.349-22G>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.865-22G>C	intron	N/A	ENSP00000268057.4	Q96RK4-1
BBS4	ENST00000395205.7	TSL:1	c.349-22G>C	intron	N/A	ENSP00000378631.3	Q96RK4-3
BBS4	ENST00000566400.6	TSL:1	c.349-22G>C	intron	N/A	ENSP00000456759.2	H3BSL3

Frequencies

GnomAD3 genomes

AF:

0.00421

AC:

640

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00112

AC:

282

AN:

251468

AF XY:

0.000714

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000406

AC:

594

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

224

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0154

AC:

517

AN:

33480

American (AMR)

AF:

0.000470

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1112010

Other (OTH)

AF:

0.000695

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00421

AC:

641

AN:

152286

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0149

AC:

621

AN:

41548

American (AMR)

AF:

0.000915

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

102

136

170

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:

0.00213

Hom.:

Bravo

AF:

0.00496

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.5

(source)

DANN

Benign

0.54

PhyloP100

-2.4

BranchPoint Hunter

1.0

PromoterAI

0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.40

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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