11-66532044-A-G

Position:

chr11-66532044-A-G

Variant summary

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

The ENST00000318312.12(BBS1):c.*7A>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 0.593 in 1,594,354 control chromosomes in the GnomAD database, including 286,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33640 hom., cov: 32)

Exomes 𝑓: 0.59 ( 253027 hom. )

Consequence

BBS1
ENST00000318312.12 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.951

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=-0.89).

BP6

Variant 11-66532044-A-G is Benign according to our data. Variant chr11-66532044-A-G is described in ClinVar as [Benign]. Clinvar id is 261745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66532044-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 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.*7A>G		3_prime_UTR_variant	17/17	ENST00000318312.12	NP_078925.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS1	ENST00000318312.12 linkuse as main transcript	c.*7A>G		3_prime_UTR_variant	17/17	1	NM_024649.5	ENSP00000317469	P1	Q8NFJ9-1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98845

AN:

151870

Hom.:

33590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.852

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.599

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.549

AC:

119075

AN:

216906

Hom.:

34523

AF XY:

0.547

AC XY:

64128

AN XY:

117242

show subpopulations

Gnomad AFR exome

AF:

0.848

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.523

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.649

Gnomad NFE exome

AF:

0.595

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.587

AC:

846816

AN:

1442366

Hom.:

253027

Cov.:

AF XY:

0.583

AC XY:

417485

AN XY:

715904

show subpopulations

Gnomad4 AFR exome

AF:

0.865

Gnomad4 AMR exome

AF:

0.367

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.502

Gnomad4 SAS exome

AF:

0.411

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.600

Gnomad4 OTH exome

AF:

0.591

GnomAD4 genome

AF:

0.651

AC:

98945

AN:

151988

Hom.:

33640

Cov.:

AF XY:

0.645

AC XY:

47909

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.853

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.599

Gnomad4 EAS

AF:

0.513

Gnomad4 SAS

AF:

0.408

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.599

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.611

Hom.:

54191

Bravo

AF:

0.649

Asia WGS

AF:

0.501

AC:

1745

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 1

Benign:7

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Jul 28, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

DANN

Benign

0.48

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