11-66510678-T-C

Variant names:

• chr11-66510678-T-C
• rs903736005
• NM_024649.5:c.19T>C

Variant summary

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

The NM_024649.5(BBS1):​c.19T>C​(p.Ser7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS1 NM_024649.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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=0.1206989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS1	NM_024649.5	c.19T>C	p.Ser7Pro	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.19T>C	p.Ser7Pro	missense_variant	Exon 1 of 17	1	NM_024649.5	ENSP00000317469.7
ENSG00000256349	ENST00000419755.3	c.159-335T>C		intron_variant	Intron 1 of 16	2		ENSP00000398526.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.15	T;.;T;.;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.55	T;T;T;T;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.6	L;.;.;L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.43	N;N;N;N;.
REVEL	Benign	0.26
Sift	Uncertain	0.016	D;D;D;T;.
Sift4G	Uncertain	0.045	D;D;D;D;T
Polyphen		0.0	B;.;B;.;.
Vest4		0.32
MutPred		0.15		Loss of phosphorylation at S7 (P = 0.0121);Loss of phosphorylation at S7 (P = 0.0121);Loss of phosphorylation at S7 (P = 0.0121);Loss of phosphorylation at S7 (P = 0.0121);Loss of phosphorylation at S7 (P = 0.0121);
MVP		0.86
MPC		0.19
ClinPred		0.075	T
GERP RS		2.3
Varity_R		0.12
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs903736005; hg19: chr11-66278149;