chr11-66520965-C-T

Variant names:

• chr11-66520965-C-T
• rs113096860
• NM_024649.5:c.724-305C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001348571.2(ZDHHC24):​c.*523G>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 0.0515 in 407,782 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (230 hom., cov: 33)
  • Exomes 𝑓: 0.051 (377 hom.)
• Consequence: ZDHHC24 NM_001348571.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.767
• Publications: 1 publications found

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]

ENSG00000256349 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-66520965-C-T is Benign according to our data. Variant chr11-66520965-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348571.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS1	NM_024649.5	MANE Select	c.724-305C>T		intron	N/A	NP_078925.3
	ZDHHC24	NM_001348571.2		c.*523G>A		3_prime_UTR	Exon 5 of 5	NP_001335500.1	E9PLR9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS1	ENST00000318312.12	TSL:1 MANE Select	c.724-305C>T		intron	N/A	ENSP00000317469.7	Q8NFJ9-1
	ENSG00000256349	ENST00000419755.3	TSL:2	c.835-305C>T		intron	N/A	ENSP00000398526.3
	BBS1	ENST00000393994.4	TSL:1	c.723+1217C>T		intron	N/A	ENSP00000377563.2	Q8NFJ9-3

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7827 AN: 152054 Hom.: 230 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0551

GnomAD4 exome AF: 0.0515 AC: 13156 AN: 255610 Hom.: 377 Cov.: 0 AF XY: 0.0505 AC XY: 6965 AN XY: 137952

African (AFR) AF: 0.0526 AC: 389 AN: 7392

American (AMR) AF: 0.0274 AC: 335 AN: 12222

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 456 AN: 6884

East Asian (EAS) AF: 0.000315 AC: 4 AN: 12684

South Asian (SAS) AF: 0.0443 AC: 1845 AN: 41648

European-Finnish (FIN) AF: 0.0553 AC: 650 AN: 11754

Middle Eastern (MID) AF: 0.0786 AC: 173 AN: 2200

European-Non Finnish (NFE) AF: 0.0584 AC: 8586 AN: 147114

Other (OTH) AF: 0.0524 AC: 718 AN: 13712

GnomAD4 genome AF: 0.0515 AC: 7830 AN: 152172 Hom.: 230 Cov.: 33 AF XY: 0.0498 AC XY: 3707 AN XY: 74396

African (AFR) AF: 0.0540 AC: 2244 AN: 41526

American (AMR) AF: 0.0382 AC: 584 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0675 AC: 234 AN: 3468

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5162

South Asian (SAS) AF: 0.0370 AC: 178 AN: 4812

European-Finnish (FIN) AF: 0.0482 AC: 511 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0575 AC: 3908 AN: 67998

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0501 Hom.: 24

Bravo AF: 0.0504

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.62
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113096860; hg19: chr11-66288436;