chr11-66521262-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000526986.5(ZDHHC24):c.*226C>G variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4629 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42799 hom. )

Consequence

ZDHHC24
ENST00000526986.5 3_prime_UTR

Scores

Splicing: ADA: 0.00005736

Clinical Significance

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

Conservation

PhyloP100: 0.690

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Myriad Women’s Health, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS1 links:

ENSG00000256349 (HGNC:):

ENSG00000256349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 96131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
BBS1	NM_024649.5 link	c.724-8G>C		splice_region_variant, intron_variant	Intron 8 of 16	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.724-8G>C		splice_region_variant, intron_variant	Intron 8 of 16	1	NM_024649.5	ENSP00000317469.7		Q8NFJ9-1
ENSG00000256349	ENST00000419755.3 link	c.835-8G>C		splice_region_variant, intron_variant	Intron 8 of 16	2		ENSP00000398526.3

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

GnomAD2 exomes

AF:

0.232

AC:

58276

AN:

251346

AF XY:

0.233

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 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

African (AFR)

AF:

0.226

AC:

7558

AN:

33428

American (AMR)

AF:

0.149

AC:

6678

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4379

AN:

26116

East Asian (EAS)

AF:

0.261

AC:

10346

AN:

39686

South Asian (SAS)

AF:

0.215

AC:

18532

AN:

86198

European-Finnish (FIN)

AF:

0.373

AC:

19928

AN:

53402

Middle Eastern (MID)

AF:

0.136

AC:

776

AN:

5714

European-Non Finnish (NFE)

AF:

0.240

AC:

265737

AN:

1109504

Other (OTH)

AF:

0.227

AC:

13691

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

12489

24978

37468

49957

62446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9022

18044

27066

36088

45110

<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:

0.240

AC:

36469

AN:

152128

Hom.:

4629

Cov.:

AF XY:

0.244

AC XY:

18147

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.230

AC:

9550

AN:

41508

American (AMR)

AF:

0.181

AC:

2773

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

522

AN:

3468

East Asian (EAS)

AF:

0.268

AC:

1387

AN:

5168

South Asian (SAS)

AF:

0.202

AC:

972

AN:

4820

European-Finnish (FIN)

AF:

0.388

AC:

4099

AN:

10564

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16472

AN:

68004

Other (OTH)

AF:

0.200

AC:

423

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1434

2868

4301

5735

7169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.194

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

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 02, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2015

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

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

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Aug 09, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.86

CADD

Benign

6.3

(source)

DANN

Benign

0.69

PhyloP100

0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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