rs10029

Positions:

chr7-116526650-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1

The ENST00000614113.5(CAV1):c.334C>T(p.Gln112*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,128 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 295 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 223 hom. )

Consequence

CAV1
ENST00000614113.5 stop_gained

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.02

Variant links:

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]

CAV1 links:

CAV1 (HGNC:):

CAV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0402 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 7-116526650-C-T is Benign according to our data. Variant chr7-116526650-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-116526650-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5 linkuse as main transcript	c.156C>T	p.Val52Val	synonymous_variant	2/3	ENST00000341049.7	NP_001744.2	Q03135-1Q2TNI1Q59E85
CAV1	NM_001172895.1 linkuse as main transcript	c.63C>T	p.Val21Val	synonymous_variant	2/3		NP_001166366.1	A0A024R757Q2TNI1Q59E85
CAV1	NM_001172896.2 linkuse as main transcript	c.63C>T	p.Val21Val	synonymous_variant	1/2		NP_001166367.1	A0A024R757Q2TNI1Q7Z4F3Q59E85
CAV1	NM_001172897.2 linkuse as main transcript	c.63C>T	p.Val21Val	synonymous_variant	2/3		NP_001166368.1	A0A024R757Q2TNI1A9XTE5Q59E85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7 linkuse as main transcript	c.156C>T	p.Val52Val	synonymous_variant	2/3	1	NM_001753.5	ENSP00000339191.2		Q03135-1

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5184

AN:

152160

Hom.:

295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.00890

AC:

2238

AN:

251354

Hom.:

124

AF XY:

0.00651

AC XY:

884

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00345

AC:

5037

AN:

1461850

Hom.:

223

Cov.:

AF XY:

0.00292

AC XY:

2123

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.00751

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00752

GnomAD4 genome

AF:

0.0341

AC:

5195

AN:

152278

Hom.:

295

Cov.:

AF XY:

0.0327

AC XY:

2435

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0384

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 17, 2023	- -

Pulmonary hypertension, primary, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.96

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over