7-116526317-TCTGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000393467.1(CAV1):c.-270_-267del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,427,130 control chromosomes in the GnomAD database, including 60 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (43 hom.)
• Consequence: CAV1 ENST00000393467.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.823

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 -10 ACMG points.

• BP6: Variant 7-116526317-TCTGC-T is Benign according to our data. Variant chr7-116526317-TCTGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1209449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00585 (890/152242) while in subpopulation EAS AF= 0.0497 (256/5150). AF 95% confidence interval is 0.0447. There are 17 homozygotes in gnomad4. There are 505 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.31-207_31-204del		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.-63-207_-63-204del		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.31-207_31-204del		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 891 AN: 152128 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00409 AC: 5211 AN: 1274888 Hom.: 43 AF XY: 0.00406 AC XY: 2518 AN XY: 620852

Gnomad4 AFR exome AF: 0.000347

Gnomad4 AMR exome AF: 0.00535

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0392

Gnomad4 SAS exome AF: 0.00235

Gnomad4 FIN exome AF: 0.0271

Gnomad4 NFE exome AF: 0.00263

Gnomad4 OTH exome AF: 0.00527

GnomAD4 genome AF: 0.00585 AC: 890 AN: 152242 Hom.: 17 Cov.: 32 AF XY: 0.00679 AC XY: 505 AN XY: 74428

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0497

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.00354

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00475 Hom.: 0

Bravo AF: 0.00445

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs61544792; hg19: chr7-116166371;