rs1357950163

Variant names:

• chr10-110900417-C-G
• NM_001195305.3:c.222G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-110900417-C-G
• chr10-110900417-C-T

Variant summary

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

The NM_001195305.3(BBIP1):​c.222G>C​(p.Gln74His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000361 in 1,383,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q74Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: BBIP1 NM_001195305.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

Genes affected

BBIP1 (HGNC:28093): (BBSome interacting protein 1) This gene encodes one of eight proteins that form the BBSome complex and is essential for its assembly. The BBSome complex is involved in trafficking signal receptors to and from the cilia. Mutations in this gene result in Bardet-Biedl syndrome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

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=0.10952532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBIP1	NM_001195305.3	c.222G>C	p.Gln74His	missense_variant	Exon 4 of 4	ENST00000448814.7	NP_001182234.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBIP1	ENST00000448814.7	c.222G>C	p.Gln74His	missense_variant	Exon 4 of 4	1	NM_001195305.3	ENSP00000436622.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000361 AC: 5 AN: 1383506 Hom.: 0 Cov.: 30 AF XY: 0.00000439 AC XY: 3 AN XY: 682702

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: 0.00000463

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	0.33
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;.;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.74	.;.;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D;D;D;.;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D;D;.;D
Sift4G	Uncertain	0.042	D;T;D;D;T
Vest4		0.12
MutPred		0.073		Loss of MoRF binding (P = 0.0975);.;.;Loss of MoRF binding (P = 0.0975);.;
MVP		0.081
ClinPred		0.96	D
GERP RS		-0.72
Varity_R		0.81

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: chr10-112660175;