rs113994178

chr11-66510645-ACGACGCCTGCGAAGATGGCCGCTGCGTCCTCATCGGATTC-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_024649.5(BBS1):c.-3_37del variant causes a start lost, 5 prime UTR change. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS1 NM_024649.5 start_lost, 5_prime_UTR
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.91

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• PP5: Variant 11-66510645-ACGACGCCTGCGAAGATGGCCGCTGCGTCCTCATCGGATTC-A is Pathogenic according to our data. Variant chr11-66510645-ACGACGCCTGCGAAGATGGCCGCTGCGTCCTCATCGGATTC-A is described in ClinVar as [Pathogenic]. Clinvar id is 21708.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBS1	NM_024649.5	c.-3_37del		start_lost, 5_prime_UTR_variant	1/17	ENST00000318312.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBS1	ENST00000318312.12	c.-3_37del		start_lost, 5_prime_UTR_variant	1/17	1	NM_024649.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Bardet-Biedl syndrome Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Invitae	Jun 13, 2022	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BBS1 protein in which other variant(s) (p.Ser16Cys) have been observed in individuals with BBS1-related conditions (PMID: 31196119). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 21708). Disruption of the initiator codon has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12524598, 17980398). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the BBS1 mRNA. The next in-frame methionine is located at codon 31. -
Pathogenic, no assertion criteria provided	curation	GeneReviews	Oct 13, 2009	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113994178; hg19: chr11-66278116;