chr11-66510673-C-G

Variant names:

• chr11-66510673-C-G
• NM_024649.5:c.14C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024649.5(BBS1):​c.14C>G​(p.Ser5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BBS1 NM_024649.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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]

ENSG00000256349 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18692127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS1	NM_024649.5	c.14C>G	p.Ser5Cys	missense_variant	Exon 1 of 17	ENST00000318312.12	NP_078925.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS1	ENST00000318312.12	c.14C>G	p.Ser5Cys	missense_variant	Exon 1 of 17	1	NM_024649.5	ENSP00000317469.7
ENSG00000256349	ENST00000419755.3	c.159-340C>G		intron_variant	Intron 1 of 16	2		ENSP00000398526.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.29	T;.;T;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.70	T;T;T;T;T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Benign	1.6	L;.;.;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N;N;N;N;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.028	D;D;D;D;.
Sift4G	Benign	0.063	T;D;D;D;D
Polyphen		0.51	P;.;P;.;.
Vest4		0.39
MutPred		0.23		Loss of phosphorylation at M5 (P = 0.0046);Loss of phosphorylation at M5 (P = 0.0046);Loss of phosphorylation at M5 (P = 0.0046);Loss of phosphorylation at M5 (P = 0.0046);Loss of phosphorylation at M5 (P = 0.0046);
MVP		0.90
MPC		0.15
ClinPred		0.23	T
GERP RS		4.0
Varity_R		0.094
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66278144;