chr10-110900422-C-T

Variant names:

• chr10-110900422-C-T
• rs2134015678
• NM_001195305.3:c.217G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195305.3(BBIP1):​c.217G>A​(p.Ala73Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A73P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBIP1 NM_001195305.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

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]

BBIP1 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 18

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20399448).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195305.3. 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
	BBIP1	NM_001195305.3	MANE Select	c.217G>A	p.Ala73Thr	missense	Exon 4 of 4	NP_001182234.1	A8MTZ0-1
	BBIP1	NM_001195306.2		c.217G>A	p.Ala73Thr	missense	Exon 4 of 4	NP_001182235.1	A8MTZ0-1
	BBIP1	NM_001243783.3		c.151G>A	p.Ala51Thr	missense	Exon 3 of 3	NP_001230712.1	A8MTZ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBIP1	ENST00000448814.7	TSL:1 MANE Select	c.217G>A	p.Ala73Thr	missense	Exon 4 of 4	ENSP00000436622.2	A8MTZ0-1
	BBIP1	ENST00000605742.5	TSL:1	c.217G>A	p.Ala73Thr	missense	Exon 4 of 4	ENSP00000474675.1	A8MTZ0-1
	BBIP1	ENST00000423273.5	TSL:1	c.142G>A	p.Ala48Thr	missense	Exon 3 of 3	ENSP00000432274.1	A8MTZ0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.68	T
PhyloP100		5.6
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.026	D
Vest4		0.39
MutPred		0.067		Gain of glycosylation at A73 (P = 0.0547)
MVP		0.12
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.86
Mutation Taster		=88/12	polymorphism

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: rs2134015678; hg19: chr10-112660180;