15-72695247-G-T

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.76+19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,532,184 control chromosomes in the GnomAD database, including 752,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68974 hom., cov: 32)

Exomes 𝑓: 0.99 ( 683269 hom. )

Consequence

BBS4
NM_033028.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.744

Publications

9 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 15-72695247-G-T is Benign according to our data. Variant chr15-72695247-G-T is described in ClinVar as Benign. ClinVar VariationId is 166733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.76+19G>T	intron	N/A	NP_149017.2
BBS4	NM_001320665.2		c.76+19G>T	intron	N/A	NP_001307594.1	H3BSL2
BBS4	NM_001252678.2		c.-446+8996G>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.76+19G>T	intron	N/A	ENSP00000268057.4	Q96RK4-1
BBS4	ENST00000395205.7	TSL:1	c.-441+8996G>T	intron	N/A	ENSP00000378631.3	Q96RK4-3
BBS4	ENST00000566400.6	TSL:1	c.-446+8996G>T	intron	N/A	ENSP00000456759.2	H3BSL3

Frequencies

GnomAD3 genomes

AF:

0.949

AC:

144340

AN:

152170

Hom.:

68946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.984

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.967

GnomAD2 exomes

AF:

0.987

AC:

247089

AN:

250462

AF XY:

0.991

show subpopulations

Gnomad AFR exome

AF:

0.813

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.995

AC:

1372637

AN:

1379896

Hom.:

683269

Cov.:

AF XY:

0.996

AC XY:

687837

AN XY:

690900

show subpopulations

African (AFR)

AF:

0.816

AC:

25940

AN:

31772

American (AMR)

AF:

0.991

AC:

44113

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

25634

AN:

25634

East Asian (EAS)

AF:

1.00

AC:

39200

AN:

39200

South Asian (SAS)

AF:

1.00

AC:

84202

AN:

84234

European-Finnish (FIN)

AF:

1.00

AC:

53223

AN:

53224

Middle Eastern (MID)

AF:

0.990

AC:

5310

AN:

5366

European-Non Finnish (NFE)

AF:

1.00

AC:

1037934

AN:

1038226

Other (OTH)

AF:

0.989

AC:

57081

AN:

57716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

269

539

808

1078

1347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19698

39396

59094

78792

98490

<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:

0.948

AC:

144419

AN:

152288

Hom.:

68974

Cov.:

AF XY:

0.950

AC XY:

70782

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.819

AC:

34010

AN:

41520

American (AMR)

AF:

0.984

AC:

15057

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5192

AN:

5192

South Asian (SAS)

AF:

1.00

AC:

4832

AN:

4834

European-Finnish (FIN)

AF:

1.00

AC:

10614

AN:

10614

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67995

AN:

68038

Other (OTH)

AF:

0.968

AC:

2044

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

336

673

1009

1346

1682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.952

Hom.:

10172

Bravo

AF:

0.941

Asia WGS

AF:

0.989

AC:

3440

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

Bardet-Biedl syndrome (1)

Bardet-Biedl syndrome 1 (1)

Bardet-Biedl syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.1

(source)

DANN

Benign

0.52

PhyloP100

0.74

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

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

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