rs3807994

Positions:

• chr7-116557525-G-A
• chr7-116557525-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001753.5(CAV1):​c.196-1421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,964 control chromosomes in the GnomAD database, including 6,116 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6116 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.196-1421G>A		intron_variant		ENST00000341049.7
CAV1	NM_001172895.1	c.103-1421G>A		intron_variant
CAV1	NM_001172896.2	c.103-1421G>A		intron_variant
CAV1	NM_001172897.2	c.103-1421G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.196-1421G>A		intron_variant		1	NM_001753.5	P3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42146 AN: 151846 Hom.: 6114 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42188 AN: 151964 Hom.: 6116 Cov.: 32 AF XY: 0.276 AC XY: 20509 AN XY: 74274

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.259

Alfa AF: 0.196 Hom.: 762

Bravo AF: 0.279

Asia WGS AF: 0.219 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.094
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3807994; hg19: chr7-116197579;