7-116525179-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001172895.1(CAV1):c.-690C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,613,894 control chromosomes in the GnomAD database, including 2,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 175 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2393 hom. )

Consequence

CAV1
NM_001172895.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.460

Publications

5 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
congenital generalized lipodystrophy type 3
Inheritance: AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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
lipodystrophy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CAV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-116525179-C-T is Benign according to our data. Variant chr7-116525179-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172895.1. 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
	CAV1	NM_001753.5	MANE Select	c.30+87C>T		intron	N/A	NP_001744.2
	CAV1	NM_001172895.1		c.-690C>T		5_prime_UTR	Exon 1 of 3	NP_001166366.1	Q59E85

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAV1	ENST00000341049.7	TSL:1 MANE Select	c.30+87C>T	intron	N/A	ENSP00000339191.2	Q03135-1
CAV1	ENST00000614113.5	TSL:1	c.30+87C>T	intron	N/A	ENSP00000479447.2	A0A7P0YWJ6
CAV1	ENST00000451122.5	TSL:1	n.117C>T	non_coding_transcript_exon	Exon 1 of 3	ENSP00000409541.1	F8WDM7

Frequencies

GnomAD3 genomes

AF:

0.0478

AC:

7272

AN:

152148

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0347

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0547

Gnomad OTH

AF:

0.0578

GnomAD2 exomes

AF:

0.0480

AC:

11833

AN:

246388

AF XY:

0.0520

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.000871

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.0524

Gnomad OTH exome

AF:

0.0530

GnomAD4 exome

AF:

0.0524

AC:

76650

AN:

1461628

Hom.:

2393

Cov.:

AF XY:

0.0544

AC XY:

39558

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.0409

AC:

1369

AN:

33480

American (AMR)

AF:

0.0266

AC:

1188

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

3210

AN:

26132

East Asian (EAS)

AF:

0.000378

AC:

AN:

39700

South Asian (SAS)

AF:

0.0854

AC:

7367

AN:

86252

European-Finnish (FIN)

AF:

0.0245

AC:

1306

AN:

53356

Middle Eastern (MID)

AF:

0.0818

AC:

472

AN:

5768

European-Non Finnish (NFE)

AF:

0.0525

AC:

58402

AN:

1111840

Other (OTH)

AF:

0.0550

AC:

3321

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

4632

9264

13897

18529

23161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2154

4308

6462

8616

10770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0478

AC:

7279

AN:

152266

Hom.:

175

Cov.:

AF XY:

0.0461

AC XY:

3431

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0406

AC:

1687

AN:

41548

American (AMR)

AF:

0.0346

AC:

530

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

407

AN:

3468

East Asian (EAS)

AF:

0.00155

AC:

AN:

5170

South Asian (SAS)

AF:

0.0901

AC:

435

AN:

4828

European-Finnish (FIN)

AF:

0.0243

AC:

258

AN:

10620

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0547

AC:

3722

AN:

68016

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

365

729

1094

1458

1823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0543

Hom.:

195

Bravo

AF:

0.0459

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

9.9

(source)

DANN

Benign

0.71

PhyloP100

-0.46

PromoterAI

0.0062

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over