rs55848325

Variant names:

• chr11-66510683-T-C
• rs55848325
• NM_024649.5:c.24T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_024649.5(BBS1):​c.24T>C​(p.Asp8Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,614,192 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (20 hom.)
• Consequence: BBS1 NM_024649.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:12
• Conservation: PhyloP100: 2.04
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-66510683-T-C is Benign according to our data. Variant chr11-66510683-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 193457.
• BP7: Synonymous conserved (PhyloP=2.04 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.24T>C	p.Asp8Asp	synonymous	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.24T>C	p.Asp8Asp	synonymous	Exon 1 of 17	ENSP00000317469.7	Q8NFJ9-1
	BBS1	ENST00000393994.4	TSL:1	c.24T>C	p.Asp8Asp	synonymous	Exon 1 of 13	ENSP00000377563.2	Q8NFJ9-3
	ENSG00000256349	ENST00000419755.3	TSL:2	c.159-330T>C		intron	N/A	ENSP00000398526.3

Frequencies

GnomAD3 genomes AF: 0.00287 AC: 437 AN: 152228 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00453

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00402 AC: 1009 AN: 250784 AF XY: 0.00425

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.0153

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.00493

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00400 AC: 5851 AN: 1461846 Hom.: 20 Cov.: 33 AF XY: 0.00417 AC XY: 3036 AN XY: 727218

African (AFR) AF: 0.000597 AC: 20 AN: 33480

American (AMR) AF: 0.00125 AC: 56 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0151 AC: 394 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00603 AC: 520 AN: 86256

European-Finnish (FIN) AF: 0.00144 AC: 77 AN: 53394

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.00403 AC: 4485 AN: 1111998

Other (OTH) AF: 0.00429 AC: 259 AN: 60394

GnomAD4 genome AF: 0.00287 AC: 437 AN: 152346 Hom.: 2 Cov.: 32 AF XY: 0.00246 AC XY: 183 AN XY: 74502

African (AFR) AF: 0.000409 AC: 17 AN: 41590

American (AMR) AF: 0.00118 AC: 18 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4830

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00453 AC: 308 AN: 68024

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00494 Hom.: 1

Bravo AF: 0.00281

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.00551

EpiControl AF: 0.00433

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	4	Bardet-Biedl syndrome 1 (5)
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Bardet-Biedl syndrome (1)
-	-	1	BBS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.66
PhyloP100		2.0
PromoterAI		-0.0067	Neutral
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55848325; hg19: chr11-66278154;