11-66520965-C-T

Position:

• chr11-66520965-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024649.5(BBS1):​c.724-305C>T variant causes a intron 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: BBS1 NM_024649.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.767

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]

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS1	NM_024649.5	c.724-305C>T		intron_variant		ENST00000318312.12	NP_078925.3
ZDHHC24	NM_001348571.2	c.*523G>A		3_prime_UTR_variant	5/5		NP_001335500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS1	ENST00000318312.12	c.724-305C>T		intron_variant		1	NM_024649.5	ENSP00000317469	P1

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

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.000315

Gnomad4 SAS exome AF: 0.0443

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0584

Gnomad4 OTH exome AF: 0.0524

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

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0370

Gnomad4 FIN AF: 0.0482

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0501 Hom.: 24

Bravo AF: 0.0504

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs113096860; hg19: chr11-66288436;