7-116525108-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001753.5(CAV1):c.30+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,614,228 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (13 hom.)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.736

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=-0.68).
• BP6: Variant 7-116525108-G-A is Benign according to our data. Variant chr7-116525108-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 995628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-116525108-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00198 (302/152356) while in subpopulation NFE AF= 0.00367 (250/68040). AF 95% confidence interval is 0.0033. There are 0 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.30+16G>A		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.-761G>A		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.30+16G>A		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 302 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00367

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00182 AC: 454 AN: 249776 Hom.: 2 AF XY: 0.00176 AC XY: 238 AN XY: 135146

Gnomad AFR exome AF: 0.000618

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.000878

Gnomad NFE exome AF: 0.00301

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00339 AC: 4959 AN: 1461872 Hom.: 13 Cov.: 31 AF XY: 0.00335 AC XY: 2438 AN XY: 727238

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00170

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.00410

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.00198 AC: 302 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74502

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00367

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00217 Hom.: 0

Bravo AF: 0.00195

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 14, 2020	- -

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	-0.68
Cadd	Benign	7.9
Dann	Benign	0.92

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: rs148066554; hg19: chr7-116165162; COSMIC: COSV61952606; COSMIC: COSV61952606;