chr11-66521254-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBS2_Supporting

The NM_001348571.2(ZDHHC24):​c.*234G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000575 in 1,602,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

ZDHHC24
NM_001348571.2 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.44
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 11-66521254-C-T is Benign according to our data. Variant chr11-66521254-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66521254-C-T is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BBS1NM_024649.5 linkc.724-16C>T intron_variant Intron 8 of 16 ENST00000318312.12 NP_078925.3 Q8NFJ9-1
ZDHHC24NM_001348571.2 linkc.*234G>A 3_prime_UTR_variant Exon 5 of 5 NP_001335500.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BBS1ENST00000318312.12 linkc.724-16C>T intron_variant Intron 8 of 16 1 NM_024649.5 ENSP00000317469.7 Q8NFJ9-1
ENSG00000256349ENST00000419755.3 linkc.835-16C>T intron_variant Intron 8 of 16 2 ENSP00000398526.3

Frequencies

GnomAD3 genomes
AF:
0.000801
AC:
122
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.0614
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000852
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000410
AC:
103
AN:
251344
Hom.:
0
AF XY:
0.000456
AC XY:
62
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000818
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000551
AC:
799
AN:
1449680
Hom.:
2
Cov.:
27
AF XY:
0.000514
AC XY:
371
AN XY:
722006
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000673
Gnomad4 OTH exome
AF:
0.000684
GnomAD4 genome
AF:
0.000801
AC:
122
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.000792
AC XY:
59
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000852
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000352
Hom.:
0
Bravo
AF:
0.00109

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Likely benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJun 20, 2024- -
Bardet-Biedl syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 03, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.3
DANN
Benign
0.62
BranchPoint Hunter
2.0

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.

Other links and lift over

dbSNP: rs141332689; hg19: chr11-66288725; COSMIC: COSV100568030; COSMIC: COSV100568030; API