rs1997623

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The ENST00000451122.5(CAV1):n.244A>C variant causes a non coding transcript exon 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
ENST00000451122.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.46

Publications

29 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

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=-0.88).

BP6

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

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 rank	MANE	Protein	UniProt
CAV1	NM_001753.5 link	c.30+214A>C		intron_variant	Intron 1 of 2	ENST00000341049.7	NP_001744.2	Q03135-1Q2TNI1Q59E85
CAV1	NM_001172895.1 link	c.-563A>C		5_prime_UTR_variant	Exon 1 of 3		NP_001166366.1	A0A024R757Q2TNI1Q59E85

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7 link	c.30+214A>C		intron_variant	Intron 1 of 2	1	NM_001753.5	ENSP00000339191.2		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

GnomAD2 exomes

AF:

0.862

AC:

131205

AN:

152164

AF XY:

0.860

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 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

African (AFR)

AF:

0.699

AC:

22144

AN:

31688

American (AMR)

AF:

0.904

AC:

32379

AN:

35820

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

21976

AN:

25186

East Asian (EAS)

AF:

0.955

AC:

34163

AN:

35782

South Asian (SAS)

AF:

0.848

AC:

67038

AN:

79078

European-Finnish (FIN)

AF:

0.877

AC:

42339

AN:

48272

Middle Eastern (MID)

AF:

0.843

AC:

4799

AN:

5694

European-Non Finnish (NFE)

AF:

0.846

AC:

913495

AN:

1079860

Other (OTH)

AF:

0.850

AC:

49321

AN:

58054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10486

20972

31458

41944

52430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20776

41552

62328

83104

103880

<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:

0.815

AC:

124058

AN:

152190

Hom.:

50947

Cov.:

AF XY:

0.818

AC XY:

60853

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.711

AC:

29503

AN:

41508

American (AMR)

AF:

0.855

AC:

13087

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.872

AC:

3027

AN:

3472

East Asian (EAS)

AF:

0.947

AC:

4881

AN:

5154

South Asian (SAS)

AF:

0.860

AC:

4140

AN:

4812

European-Finnish (FIN)

AF:

0.879

AC:

9328

AN:

10616

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.843

AC:

57360

AN:

68006

Other (OTH)

AF:

0.824

AC:

1737

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1162

2324

3487

4649

5811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.829

Hom.:

14054

Bravo

AF:

0.810

Asia WGS

AF:

0.885

AC:

3077

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Congenital generalized lipodystrophy type 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pulmonary hypertension, primary, 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.3

(source)

DANN

Benign

0.46

PhyloP100

-1.5

PromoterAI

-0.013

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over