7-116526346-C-T

Variant summary

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

The ENST00000393467.1(CAV1):c.-242C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,477,908 control chromosomes in the GnomAD database, including 4,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (312 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4330 hom.)
• Consequence: CAV1 ENST00000393467.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0640

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=-0.64).
• BP6: Variant 7-116526346-C-T is Benign according to our data. Variant chr7-116526346-C-T is described in ClinVar as [Benign]. Clinvar id is 1275203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.31-179C>T		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.-63-179C>T		intron_variant
CAV1	NM_001172896.2			upstream_gene_variant
CAV1	NM_001172897.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.31-179C>T		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8134 AN: 152126 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0678

GnomAD4 exome AF: 0.0761 AC: 100934 AN: 1325666 Hom.: 4330 Cov.: 31 AF XY: 0.0747 AC XY: 48440 AN XY: 648524

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.0472

Gnomad4 ASJ exome AF: 0.0666

Gnomad4 EAS exome AF: 0.0000867

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0672

Gnomad4 NFE exome AF: 0.0860

Gnomad4 OTH exome AF: 0.0678

GnomAD4 genome AF: 0.0534 AC: 8130 AN: 152242 Hom.: 312 Cov.: 32 AF XY: 0.0510 AC XY: 3792 AN XY: 74420

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0197

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0676 Hom.: 79

Bravo AF: 0.0525

Asia WGS AF: 0.0100 AC: 37 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 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	15
Dann	Benign	0.90

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: rs56014347; hg19: chr7-116166400;