rs147202164

Positions:

chr15-72735954-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033028.5(BBS4):c.1236A>T(p.Glu412Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,128 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 13 hom. )

Consequence

BBS4
NM_033028.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.645

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:

BBS4 (HGNC:):

BBS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062256753).

BP6

Variant 15-72735954-A-T is Benign according to our data. Variant chr15-72735954-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 262136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-72735954-A-T is described in Lovd as [Benign]. Variant chr15-72735954-A-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS4	NM_033028.5 linkuse as main transcript	c.1236A>T	p.Glu412Asp	missense_variant	14/16	ENST00000268057.9	NP_149017.2	Q96RK4-1A0A0S2Z3A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS4	ENST00000268057.9 linkuse as main transcript	c.1236A>T	p.Glu412Asp	missense_variant	14/16	1	NM_033028.5	ENSP00000268057.4		Q96RK4-1

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00166

AC:

417

AN:

251412

Hom.:

AF XY:

0.00205

AC XY:

278

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00715

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00122

AC:

1780

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1036

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00728

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000851

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.000873

AC:

133

AN:

152278

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00807

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000782

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00170

AC:

207

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00136

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 04, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	BBS4: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Bardet-Biedl syndrome 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 13, 2018

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.8

DANN

Benign

0.84

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

.;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.26

.;N

REVEL

Benign

0.12

Sift

Benign

0.63

.;T

Sift4G

Benign

0.61

T;T

Polyphen

0.0

.;B

Vest4

0.19

MutPred

0.54

.;Loss of helix (P = 0.079);

MVP

0.47

MPC

0.012

ClinPred

0.0081

GERP RS

-1.6

Varity_R

0.066

gMVP

0.12

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