Variant rs80334351 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.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

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=-0.61).

BP6

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS4	NM_033028.5 link	c.405+17C>T		intron_variant		ENST00000268057.9	NP_149017.2	Q96RK4-1A0A0S2Z3A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS4	ENST00000268057.9 link	c.405+17C>T		intron_variant		1	NM_033028.5	ENSP00000268057.4		Q96RK4-1

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

GnomAD3 exomes

AF:

0.0437

AC:

10459

AN:

239186

Hom.:

487

AF XY:

0.0406

AC XY:

5246

AN XY:

129128

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 SAS exome

AF:

0.0387

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

Gnomad4 AFR exome

AF:

0.00524

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0318

Gnomad4 EAS exome

AF:

0.000786

Gnomad4 SAS exome

AF:

0.0398

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.0260

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.0256

AC:

3906

AN:

152306

Hom.:

104

Cov.:

AF XY:

0.0271

AC XY:

2020

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.0733

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.0340

Gnomad4 NFE

AF:

0.0272

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0280

Hom.:

Bravo

AF:

0.0292

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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