Variant rs75847960 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS4	NM_033028.5 linkuse as main transcript	c.1451-45T>C		intron_variant		ENST00000268057.9	NP_149017.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS4	ENST00000268057.9 linkuse as main transcript	c.1451-45T>C		intron_variant		1	NM_033028.5	ENSP00000268057	P1	Q96RK4-1

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

GnomAD3 exomes

AF:

0.0813

AC:

16024

AN:

196986

Hom.:

741

AF XY:

0.0842

AC XY:

8815

AN XY:

104696

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 SAS exome

AF:

0.0846

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

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.0506

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.0897

Gnomad4 FIN exome

AF:

0.0549

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.0849

AC:

12924

AN:

152260

Hom.:

668

Cov.:

AF XY:

0.0810

AC XY:

6027

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0541

Gnomad4 AMR

AF:

0.0610

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0810

Gnomad4 FIN

AF:

0.0603

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.0852

Alfa

AF:

0.0977

Hom.:

126

Bravo

AF:

0.0830

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Bardet-Biedl syndrome

Benign:1

Benign, no assertion criteria provided

curation

GeneReviews

Oct 13, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.87

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over