rs1997623

chr7-116525306-A-Cchr7-116525306-A-Gchr7-116525306-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001753.5(CAV1):c.30+214A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,551,624 control chromosomes in the GnomAD database, including 555,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 50947 hom., cov: 32)

Exomes 𝑓: 0.85 ( 504968 hom. )

Consequence

CAV1
NM_001753.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-116525306-A-C is Benign according to our data. Variant chr7-116525306-A-C is described in ClinVar as [Benign]. Clinvar id is 672478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-116525306-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5 linkuse as main transcript	c.30+214A>C		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1 linkuse as main transcript	c.-563A>C		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7 linkuse as main transcript	c.30+214A>C		intron_variant		1	NM_001753.5	P3	Q03135-1

Frequencies

GnomAD3 genomes

AF:

0.815

AC:

123978

AN:

152072

Hom.:

50922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.711

Gnomad AMI

AF:

0.843

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.872

Gnomad EAS

AF:

0.947

Gnomad SAS

AF:

0.860

Gnomad FIN

AF:

0.879

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.843

Gnomad OTH

AF:

0.824

GnomAD3 exomes

AF:

0.862

AC:

131205

AN:

152164

Hom.:

56785

AF XY:

0.860

AC XY:

70663

AN XY:

82170

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.909

Gnomad ASJ exome

AF:

0.878

Gnomad EAS exome

AF:

0.949

Gnomad SAS exome

AF:

0.846

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.844

Gnomad OTH exome

AF:

0.865

GnomAD4 exome

AF:

0.849

AC:

1187654

AN:

1399434

Hom.:

504968

Cov.:

AF XY:

0.849

AC XY:

586089

AN XY:

690722

show subpopulations

Gnomad4 AFR exome

AF:

0.699

Gnomad4 AMR exome

AF:

0.904

Gnomad4 ASJ exome

AF:

0.873

Gnomad4 EAS exome

AF:

0.955

Gnomad4 SAS exome

AF:

0.848

Gnomad4 FIN exome

AF:

0.877

Gnomad4 NFE exome

AF:

0.846

Gnomad4 OTH exome

AF:

0.850

GnomAD4 genome

AF:

0.815

AC:

124058

AN:

152190

Hom.:

50947

Cov.:

AF XY:

0.818

AC XY:

60853

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.855

Gnomad4 ASJ

AF:

0.872

Gnomad4 EAS

AF:

0.947

Gnomad4 SAS

AF:

0.860

Gnomad4 FIN

AF:

0.879

Gnomad4 NFE

AF:

0.843

Gnomad4 OTH

AF:

0.824

Alfa

AF:

0.829

Hom.:

14054

Bravo

AF:

0.810

Asia WGS

AF:

0.885

AC:

3077

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital generalized lipodystrophy type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Pulmonary hypertension, primary, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

1.3

Dann

Benign

0.46

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