7-116525179-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001753.5(CAV1):c.30+87C>T variant causes a intron 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_001753.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.460

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 -14 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 id is 1232819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.30+87C>T		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.-690C>T		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.30+87C>T		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7272 AN: 152148 Hom.: 175 Cov.: 33

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

GnomAD3 exomes AF: 0.0480 AC: 11833 AN: 246388 Hom.: 420 AF XY: 0.0520 AC XY: 6963 AN XY: 134000

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 SAS exome AF: 0.0843

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.: 32 AF XY: 0.0544 AC XY: 39558 AN XY: 727106

Gnomad4 AFR exome AF: 0.0409

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.0854

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0525

Gnomad4 OTH exome AF: 0.0550

GnomAD4 genome AF: 0.0478 AC: 7279 AN: 152266 Hom.: 175 Cov.: 33 AF XY: 0.0461 AC XY: 3431 AN XY: 74456

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0901

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0563 Hom.: 135

Bravo AF: 0.0459

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	9.9
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs45498702; hg19: chr7-116165233; COSMIC: COSV61952557; COSMIC: COSV61952557;