rs2298806

Variant names:

• chr11-66514624-G-A
• rs2298806
• NM_024649.5:c.378G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_024649.5(BBS1):​c.378G>A​(p.Leu126Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,613,210 control chromosomes in the GnomAD database, including 45,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3877 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42057 hom.)
• Consequence: BBS1 NM_024649.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 1.14
• Publications: 31 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.137).
• BP6: Variant 11-66514624-G-A is Benign according to our data. Variant chr11-66514624-G-A is described in ClinVar as Benign. ClinVar VariationId is 261750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

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.378G>A	p.Leu126Leu	synonymous	Exon 4 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.378G>A	p.Leu126Leu	synonymous	Exon 4 of 17	ENSP00000317469.7	Q8NFJ9-1
	ENSG00000256349	ENST00000419755.3	TSL:2	c.489G>A	p.Leu163Leu	synonymous	Exon 4 of 17	ENSP00000398526.3
	BBS1	ENST00000393994.4	TSL:1	c.378G>A	p.Leu126Leu	synonymous	Exon 4 of 13	ENSP00000377563.2	Q8NFJ9-3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32259 AN: 151952 Hom.: 3870 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.179

GnomAD2 exomes AF: 0.224 AC: 56195 AN: 250730 AF XY: 0.227

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.379

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.235 AC: 344006 AN: 1461140 Hom.: 42057 Cov.: 35 AF XY: 0.236 AC XY: 171356 AN XY: 726920

African (AFR) AF: 0.126 AC: 4208 AN: 33480

American (AMR) AF: 0.144 AC: 6421 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4382 AN: 26134

East Asian (EAS) AF: 0.261 AC: 10358 AN: 39698

South Asian (SAS) AF: 0.215 AC: 18517 AN: 86254

European-Finnish (FIN) AF: 0.372 AC: 19659 AN: 52810

Middle Eastern (MID) AF: 0.132 AC: 761 AN: 5768

European-Non Finnish (NFE) AF: 0.240 AC: 266365 AN: 1111896

Other (OTH) AF: 0.221 AC: 13335 AN: 60376

GnomAD4 genome AF: 0.212 AC: 32278 AN: 152070 Hom.: 3877 Cov.: 32 AF XY: 0.217 AC XY: 16144 AN XY: 74338

African (AFR) AF: 0.135 AC: 5613 AN: 41490

American (AMR) AF: 0.170 AC: 2600 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1383 AN: 5160

South Asian (SAS) AF: 0.202 AC: 976 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4083 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16457 AN: 67974

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.219 Hom.: 7199

Bravo AF: 0.191

Asia WGS AF: 0.239 AC: 831 AN: 3478

EpiCase AF: 0.222

EpiControl AF: 0.228

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Bardet-Biedl syndrome 1 (6)
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		1.1
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2298806; hg19: chr11-66282095; COSMIC: COSV59147579; COSMIC: COSV59147579;