rs797044871

Positions:

• chr7-116559227-CTT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_001753.5(CAV1):​c.479_480del​(p.Phe160Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAV1 NM_001753.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 7.67

Genes affected

CAV1 (HGNC:1527): (caveolin 1) The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. Caveolin 1 and caveolin 2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. Mutations in this gene have been associated with Berardinelli-Seip congenital lipodystrophy. Alternatively spliced transcripts encode alpha and beta isoforms of caveolin 1.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 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 0.11 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-116559227-CTT-C is Pathogenic according to our data. Variant chr7-116559227-CTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 208669.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.479_480del	p.Phe160Ter	frameshift_variant	3/3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.386_387del	p.Phe129Ter	frameshift_variant	3/3		NP_001166366.1
CAV1	NM_001172896.2	c.386_387del	p.Phe129Ter	frameshift_variant	2/2		NP_001166367.1
CAV1	NM_001172897.2	c.386_387del	p.Phe129Ter	frameshift_variant	3/3		NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.479_480del	p.Phe160Ter	frameshift_variant	3/3	1	NM_001753.5	ENSP00000339191	P3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

-

POSITIVE: Relevant Alteration(s) Detected -

Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2015

- -

Congenital generalized lipodystrophy type 3;C3809192:Pulmonary hypertension, primary, 3 Pathogenic:1

Pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

May 19, 2015

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs797044871; hg19: chr7-116199281;