7-116525409-T-C

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+317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,458,810 control chromosomes in the GnomAD database, including 523,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (50982 hom., cov: 32)
  • Exomes 𝑓: 0.85 (472427 hom.)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.56

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=-0.81).
• BP6: Variant 7-116525409-T-C is Benign according to our data. Variant chr7-116525409-T-C is described in ClinVar as [Benign]. Clinvar id is 673350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.30+317T>C		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.-460T>C		5_prime_UTR_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.30+317T>C		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123983 AN: 151978 Hom.: 50956 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.824

GnomAD4 exome AF: 0.850 AC: 1110134 AN: 1306714 Hom.: 472427 Cov.: 57 AF XY: 0.850 AC XY: 541451 AN XY: 637268

Gnomad4 AFR exome AF: 0.699

Gnomad4 AMR exome AF: 0.904

Gnomad4 ASJ exome AF: 0.872

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.854

Gnomad4 FIN exome AF: 0.878

Gnomad4 NFE exome AF: 0.847

Gnomad4 OTH exome AF: 0.851

GnomAD4 genome AF: 0.816 AC: 124064 AN: 152096 Hom.: 50982 Cov.: 32 AF XY: 0.819 AC XY: 60871 AN XY: 74356

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.824

Alfa AF: 0.840 Hom.: 46025

Bravo AF: 0.810

Asia WGS AF: 0.885 AC: 3078 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

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.73

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: rs2742125; hg19: chr7-116165463; COSMIC: COSV61954378; COSMIC: COSV61954378;