chr11-66529892-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_024649.5(BBS1):c.1413C>T(p.Leu471Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,607,944 control chromosomes in the GnomAD database, including 43,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L471L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 3319 hom., cov: 31)

Exomes 𝑓: 0.23 ( 40111 hom. )

Consequence

BBS1
NM_024649.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.745

Publications

38 publications found

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:

ENSG00000256349 (HGNC:):

ENSG00000256349 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 was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 11-66529892-C-T is Benign according to our data. Variant chr11-66529892-C-T is described in ClinVar as [Benign]. Clinvar id is 261747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.745 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS1	NM_024649.5 link	c.1413C>T	p.Leu471Leu	synonymous_variant	Exon 14 of 17	ENST00000318312.12	NP_078925.3	Q8NFJ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS1	ENST00000318312.12 link	c.1413C>T	p.Leu471Leu	synonymous_variant	Exon 14 of 17	1	NM_024649.5	ENSP00000317469.7		Q8NFJ9-1
ENSG00000256349	ENST00000419755.3 link	c.1524C>T	p.Leu508Leu	synonymous_variant	Exon 14 of 17	2		ENSP00000398526.3

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27417

AN:

151950

Hom.:

3314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.158

GnomAD2 exomes

AF:

0.203

AC:

49593

AN:

244460

AF XY:

0.210

show subpopulations

Gnomad AFR exome

AF:

0.0376

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.228

AC:

332334

AN:

1455876

Hom.:

40111

Cov.:

AF XY:

0.229

AC XY:

165949

AN XY:

724504

show subpopulations

African (AFR)

AF:

0.0347

AC:

1162

AN:

33476

American (AMR)

AF:

0.136

AC:

6080

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4360

AN:

26122

East Asian (EAS)

AF:

0.132

AC:

5232

AN:

39678

South Asian (SAS)

AF:

0.207

AC:

17873

AN:

86234

European-Finnish (FIN)

AF:

0.372

AC:

17819

AN:

47842

Middle Eastern (MID)

AF:

0.130

AC:

748

AN:

5768

European-Non Finnish (NFE)

AF:

0.240

AC:

266560

AN:

1111772

Other (OTH)

AF:

0.207

AC:

12500

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16464

32928

49392

65856

82320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8896

17792

26688

35584

44480

<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:

0.180

AC:

27429

AN:

152068

Hom.:

3319

Cov.:

AF XY:

0.186

AC XY:

13815

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0429

AC:

1783

AN:

41518

American (AMR)

AF:

0.156

AC:

2386

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

520

AN:

3472

East Asian (EAS)

AF:

0.131

AC:

678

AN:

5162

South Asian (SAS)

AF:

0.194

AC:

934

AN:

4810

European-Finnish (FIN)

AF:

0.387

AC:

4086

AN:

10556

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16443

AN:

67962

Other (OTH)

AF:

0.155

AC:

328

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1078

2155

3233

4310

5388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.210

Hom.:

9989

Bravo

AF:

0.155

Asia WGS

AF:

0.173

AC:

602

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.229

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 1

Benign:4

Jun 02, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Sep 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 18, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The BBS1 c.1413C>T (p.Leu471Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a polymorphism outcome for this variant along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 24241/116022 control chromosomes (2812 homozygotes) at a frequency of 0.2089345, which greatly exceeds the estimated maximal expected allele frequency of a pathogenic BBS1 variant (0.0009449), suggesting this variant is likely a benign polymorphism. A clinical diagnostic laboratory ant at least one publication classified this variant as benign. Taken together, this variant is classified as benign. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Bardet-Biedl syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.83

(source)

DANN

Benign

0.92

PhyloP100

-0.74

Mutation Taster

=99/1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over