7-116525306-A-C

Position:

• chr7-116525306-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001753.5(CAV1):​c.30+214A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 1,551,624 control chromosomes in the GnomAD database, including 555,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50947 hom., cov: 32)
  • Exomes 𝑓: 0.85 (504968 hom.)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.46

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=-0.88).
• BP6: Variant 7-116525306-A-C is Benign according to our data. Variant chr7-116525306-A-C is described in ClinVar as [Benign]. Clinvar id is 672478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-116525306-A-C is described in Lovd as [Benign].
• 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	Protein	UniProt
CAV1	NM_001753.5	c.30+214A>C		intron_variant		ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.-563A>C		5_prime_UTR_variant	1/3		NP_001166366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.30+214A>C		intron_variant		1	NM_001753.5	ENSP00000339191	P3

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123978 AN: 152072 Hom.: 50922 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.824

GnomAD3 exomes AF: 0.862 AC: 131205 AN: 152164 Hom.: 56785 AF XY: 0.860 AC XY: 70663 AN XY: 82170

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.909

Gnomad ASJ exome AF: 0.878

Gnomad EAS exome AF: 0.949

Gnomad SAS exome AF: 0.846

Gnomad FIN exome AF: 0.882

Gnomad NFE exome AF: 0.844

Gnomad OTH exome AF: 0.865

GnomAD4 exome AF: 0.849 AC: 1187654 AN: 1399434 Hom.: 504968 Cov.: 60 AF XY: 0.849 AC XY: 586089 AN XY: 690722

Gnomad4 AFR exome AF: 0.699

Gnomad4 AMR exome AF: 0.904

Gnomad4 ASJ exome AF: 0.873

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.848

Gnomad4 FIN exome AF: 0.877

Gnomad4 NFE exome AF: 0.846

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.815 AC: 124058 AN: 152190 Hom.: 50947 Cov.: 32 AF XY: 0.818 AC XY: 60853 AN XY: 74378

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.855

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.824

Alfa AF: 0.829 Hom.: 14054

Bravo AF: 0.810

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital generalized lipodystrophy type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Pulmonary hypertension, primary, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.46

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: rs1997623; hg19: chr7-116165360; COSMIC: COSV61952832; COSMIC: COSV61952832;