Variant chr11-66520965-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024649.5(BBS1):c.724-305C>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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.767

Variant links:

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]

BBS1 links:

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:

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=-0.91).

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 linkuse as main transcript	c.724-305C>T		intron_variant		ENST00000318312.12	NP_078925.3
ZDHHC24	NM_001348571.2 linkuse as main transcript	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 linkuse as main transcript	c.724-305C>T		intron_variant		1	NM_024649.5	ENSP00000317469	P1	Q8NFJ9-1

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7827

AN:

152054

Hom.:

230

Cov.:

show subpopulations

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.:

AF XY:

0.0505

AC XY:

6965

AN XY:

137952

show subpopulations

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.:

AF XY:

0.0498

AC XY:

3707

AN XY:

74396

show subpopulations

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.:

Bravo

AF:

0.0504

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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