7-116525106-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001753.5(CAV1):c.30+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,614,164 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 33)
  • Exomes 𝑓: 0.014 (394 hom.)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.221

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-116525106-G-T is Benign according to our data. Variant chr7-116525106-G-T is described in ClinVar as [Benign]. Clinvar id is 379541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-116525106-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.30+14G>T		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.-763G>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.30+14G>T		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1692 AN: 152178 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0172 AC: 4299 AN: 249718 Hom.: 125 AF XY: 0.0201 AC XY: 2719 AN XY: 135130

Gnomad AFR exome AF: 0.00427

Gnomad AMR exome AF: 0.0115

Gnomad ASJ exome AF: 0.0224

Gnomad EAS exome AF: 0.00299

Gnomad SAS exome AF: 0.0708

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0179

GnomAD4 exome AF: 0.0142 AC: 20702 AN: 1461868 Hom.: 394 Cov.: 31 AF XY: 0.0160 AC XY: 11662 AN XY: 727232

Gnomad4 AFR exome AF: 0.00385

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.00622

Gnomad4 SAS exome AF: 0.0674

Gnomad4 FIN exome AF: 0.00234

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0111 AC: 1689 AN: 152296 Hom.: 22 Cov.: 33 AF XY: 0.0118 AC XY: 877 AN XY: 74476

Gnomad4 AFR AF: 0.00397

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.00940 Hom.: 7

Bravo AF: 0.00966

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2015

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. -

Pulmonary hypertension, primary, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	5.5
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs35697540; hg19: chr7-116165160; COSMIC: COSV61954066; COSMIC: COSV61954066;