rs3807992

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001753.5(CAV1):​c.196-1755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,162 control chromosomes in the GnomAD database, including 6,143 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6143 hom., cov: 32)

Consequence

CAV1
NM_001753.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.472

Publications

44 publications found
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 Gene-Disease associations (from GenCC):
  • pulmonary arterial hypertension
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • pulmonary hypertension, primary, 3
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • congenital generalized lipodystrophy type 3
    Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P
  • heritable pulmonary arterial hypertension
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Berardinelli-Seip congenital lipodystrophy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • amyotrophic lateral sclerosis
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAV1NM_001753.5 linkc.196-1755G>A intron_variant Intron 2 of 2 ENST00000341049.7 NP_001744.2 Q03135-1Q2TNI1Q59E85
CAV1NM_001172895.1 linkc.103-1755G>A intron_variant Intron 2 of 2 NP_001166366.1 A0A024R757Q2TNI1Q59E85
CAV1NM_001172896.2 linkc.103-1755G>A intron_variant Intron 1 of 1 NP_001166367.1 A0A024R757Q2TNI1Q7Z4F3Q59E85
CAV1NM_001172897.2 linkc.103-1755G>A intron_variant Intron 2 of 2 NP_001166368.1 A0A024R757Q2TNI1A9XTE5Q59E85

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAV1ENST00000341049.7 linkc.196-1755G>A intron_variant Intron 2 of 2 1 NM_001753.5 ENSP00000339191.2 Q03135-1

Frequencies

GnomAD3 genomes
AF:
0.278
AC:
42223
AN:
152044
Hom.:
6141
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.365
Gnomad AMI
AF:
0.280
Gnomad AMR
AF:
0.228
Gnomad ASJ
AF:
0.249
Gnomad EAS
AF:
0.220
Gnomad SAS
AF:
0.261
Gnomad FIN
AF:
0.278
Gnomad MID
AF:
0.247
Gnomad NFE
AF:
0.243
Gnomad OTH
AF:
0.263
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.278
AC:
42265
AN:
152162
Hom.:
6143
Cov.:
32
AF XY:
0.276
AC XY:
20563
AN XY:
74398
show subpopulations
African (AFR)
AF:
0.365
AC:
15133
AN:
41474
American (AMR)
AF:
0.228
AC:
3488
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.249
AC:
865
AN:
3470
East Asian (EAS)
AF:
0.220
AC:
1141
AN:
5182
South Asian (SAS)
AF:
0.260
AC:
1252
AN:
4818
European-Finnish (FIN)
AF:
0.278
AC:
2950
AN:
10606
Middle Eastern (MID)
AF:
0.252
AC:
74
AN:
294
European-Non Finnish (NFE)
AF:
0.243
AC:
16557
AN:
68002
Other (OTH)
AF:
0.260
AC:
550
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1579
3158
4736
6315
7894
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
428
856
1284
1712
2140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.257
Hom.:
701
Bravo
AF:
0.279
Asia WGS
AF:
0.219
AC:
765
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.6
DANN
Benign
0.42
PhyloP100
0.47
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3807992; hg19: chr7-116197245; API