11-66529828-G-A

Position:

chr11-66529828-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000318312.12(BBS1):c.1349G>A(p.Arg450Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00371 in 1,611,024 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R450W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.020 ( 90 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 103 hom. )

Consequence

BBS1
ENST00000318312.12 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.01

Variant links:

Genes affected

BBS1 (HGNC:966): (Bardet-Biedl syndrome 1) Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

BBS1 links:

ZDHHC24 (HGNC:27387): (zinc finger DHHC-type containing 24) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC24 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 (MetaRNN=0.0029770434).

BP6

Variant 11-66529828-G-A is Benign according to our data. Variant chr11-66529828-G-A is described in ClinVar as [Benign]. Clinvar id is 194431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66529828-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS1	NM_024649.5 linkuse as main transcript	c.1349G>A	p.Arg450Gln	missense_variant	14/17	ENST00000318312.12	NP_078925.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS1	ENST00000318312.12 linkuse as main transcript	c.1349G>A	p.Arg450Gln	missense_variant	14/17	1	NM_024649.5	ENSP00000317469	P1	Q8NFJ9-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2997

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0683

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00787

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0178

GnomAD3 exomes

AF:

0.00540

AC:

1341

AN:

248268

Hom.:

AF XY:

0.00382

AC XY:

513

AN XY:

134468

show subpopulations

Gnomad AFR exome

AF:

0.0710

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00203

AC:

2968

AN:

1459020

Hom.:

103

Cov.:

AF XY:

0.00172

AC XY:

1247

AN XY:

725982

show subpopulations

Gnomad4 AFR exome

AF:

0.0703

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00426

GnomAD4 genome

AF:

0.0198

AC:

3011

AN:

152004

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1405

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0685

Gnomad4 AMR

AF:

0.00779

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.00389

Hom.:

Bravo

AF:

0.0229

ESP6500AA

AF:

0.0668

AC:

294

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00664

AC:

806

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 02, 2017	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 17, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

.;T;T;.

Eigen

Benign

-0.057

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;D;D;D

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.1

.;L;.;.

MutationTaster

Benign

1.0

D;D;N;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.093

T;T;T;T

Polyphen

0.17, 0.60

.;B;P;.

Vest4

0.21

MVP

0.92

MPC

0.18

ClinPred

0.0090

GERP RS

3.5

Varity_R

0.27

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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