10-110900433-A-AT

Variant names:

• chr10-110900433-A-AT
• rs2134015708
• NM_001195305.3:c.205dupA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001195305.3(BBIP1):​c.205dupA​(p.Met69AsnfsTer29) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBIP1 NM_001195305.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.265 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.205dupA	p.Met69AsnfsTer29	frameshift	Exon 4 of 4	NP_001182234.1	A8MTZ0-1
	BBIP1	NM_001195306.2		c.205dupA	p.Met69AsnfsTer29	frameshift	Exon 4 of 4	NP_001182235.1	A8MTZ0-1
	BBIP1	NM_001243783.3		c.139dupA	p.Met47AsnfsTer29	frameshift	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.205dupA	p.Met69AsnfsTer29	frameshift	Exon 4 of 4	ENSP00000436622.2	A8MTZ0-1
	BBIP1	ENST00000605742.5	TSL:1	c.205dupA	p.Met69AsnfsTer29	frameshift	Exon 4 of 4	ENSP00000474675.1	A8MTZ0-1
	BBIP1	ENST00000423273.5	TSL:1	c.130dupA	p.Met44AsnfsTer29	frameshift	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
PhyloP100		5.8

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: rs2134015708; hg19: chr10-112660191;