Variant chr7-116525120-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001753.5(CAV1):c.30+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,614,140 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 39 hom., cov: 33)

Exomes 𝑓: 0.032 ( 834 hom. )

Consequence

CAV1
NM_001753.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.24

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 7-116525120-C-T is Benign according to our data. Variant chr7-116525120-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1211194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0226 (3443/152290) while in subpopulation NFE AF= 0.0351 (2386/68030). AF 95% confidence interval is 0.0339. There are 39 homozygotes in gnomad4. There are 1642 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5 linkuse as main transcript	c.30+28C>T		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1 linkuse as main transcript	c.-749C>T		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+28C>T		intron_variant		1	NM_001753.5	P3	Q03135-1

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3440

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00784

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.0167

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0351

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0231

AC:

5771

AN:

249554

Hom.:

AF XY:

0.0246

AC XY:

3321

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.00661

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0290

Gnomad FIN exome

AF:

0.0169

Gnomad NFE exome

AF:

0.0334

Gnomad OTH exome

AF:

0.0255

GnomAD4 exome

AF:

0.0315

AC:

46116

AN:

1461850

Hom.:

834

Cov.:

AF XY:

0.0316

AC XY:

22959

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00633

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0355

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0226

AC:

3443

AN:

152290

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1642

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00782

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0307

Gnomad4 FIN

AF:

0.0167

Gnomad4 NFE

AF:

0.0351

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0296

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

DANN

Benign

0.89

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