rs8432

chr11-66532044-A-G

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.*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 NM_024649.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.951

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=-0.89).
• 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	UniProt
BBS1	NM_024649.5	c.*7A>G		3_prime_UTR_variant	17/17	ENST00000318312.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS1	ENST00000318312.12	c.*7A>G		3_prime_UTR_variant	17/17	1	NM_024649.5	P1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98845 AN: 151870 Hom.: 33590 Cov.: 32

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

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.: 48 AF XY: 0.583 AC XY: 417485 AN XY: 715904

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.: 32 AF XY: 0.645 AC XY: 47909 AN XY: 74284

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:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bardet-Biedl syndrome 1 Benign:7

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

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

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

Other links and lift over

dbSNP: rs8432; hg19: chr11-66299515; COSMIC: COSV59153140; COSMIC: COSV59153140;