11-66521262-G-C

Position:

chr11-66521262-G-C

Variant summary

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

The NM_024649.5(BBS1):c.724-8G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,611,188 control chromosomes in the GnomAD database, including 47,428 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4629 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42799 hom. )

Consequence

BBS1
NM_024649.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005736

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.690

Variant links:

Genes affected

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:

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:

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=-0.86).

BP6

Variant 11-66521262-G-C is Benign according to our data. Variant chr11-66521262-G-C is described in ClinVar as [Benign]. Clinvar id is 96131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66521262-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS1	NM_024649.5 linkuse as main transcript	c.724-8G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000318312.12
ZDHHC24	NM_001348571.2 linkuse as main transcript	c.*226C>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS1	ENST00000318312.12 linkuse as main transcript	c.724-8G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_024649.5	P1	Q8NFJ9-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36436

AN:

152010

Hom.:

4621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.255

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.232

AC:

58276

AN:

251346

Hom.:

7304

AF XY:

0.233

AC XY:

31687

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.238

AC:

347625

AN:

1459060

Hom.:

42799

Cov.:

AF XY:

0.238

AC XY:

172899

AN XY:

726058

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.240

AC:

36469

AN:

152128

Hom.:

4629

Cov.:

AF XY:

0.244

AC XY:

18147

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.194

Hom.:

1044

Bravo

AF:

0.223

Asia WGS

AF:

0.245

AC:

850

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.229

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 1

Benign:7

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 09, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
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

-0.86

CADD

Benign

6.3

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

dbscSNV1_RF

Benign

0.0020

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