rs1306821707

Variant names:

• chr11-66510660-A-C
• rs1306821707
• NM_024649.5:c.1A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-66510660-A-C
• chr11-66510660-A-G
• chr11-66510660-A-T

Variant summary

Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PVS1 PS1_Moderate PM2 PP5

The NM_024649.5(BBS1):​c.1A>C​(p.Met1?) variant causes a initiator codon change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS1 NM_024649.5 initiator_codon
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.29
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• BBS1-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000256349 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 13 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 17 pathogenic variants. Next in-frame start position is after 31 codons. Genomic position: 66511056. Lost 0.051 part of the original CDS.
• PS1: Another start lost variant in NM_024649.5 (BBS1) was described as [Pathogenic] in ClinVar
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-66510660-A-C is Pathogenic according to our data. Variant chr11-66510660-A-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 555491.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024649.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS1	NM_024649.5	MANE Select	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 17	NP_078925.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBS1	ENST00000318312.12	TSL:1 MANE Select	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 17	ENSP00000317469.7	Q8NFJ9-1
	BBS1	ENST00000393994.4	TSL:1	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 13	ENSP00000377563.2	Q8NFJ9-3
	ENSG00000256349	ENST00000419755.3	TSL:2	c.159-353A>C		intron	N/A	ENSP00000398526.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Bardet-Biedl syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.70	D
PhyloP100		4.3
PROVEAN	Benign	-0.82	N
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.65	P
Vest4		0.96
MutPred		0.98		Gain of stability (P = 0.0742)
MVP		0.85
ClinPred		0.85	D
GERP RS		5.0
PromoterAI		-0.98	Under-expression
Varity_R		0.97
gMVP		0.44
Mutation Taster		=6/194	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1306821707; hg19: chr11-66278131;