rs3801994

Variant names:

• chr7-116550415-G-A
• rs3801994
• NM_001753.5:c.196-8531G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001753.5(CAV1):​c.196-8531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 152,092 control chromosomes in the GnomAD database, including 657 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 0.073 (657 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 6 publications found

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]

CAV1 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pulmonary hypertension, primary, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital generalized lipodystrophy type 3

  Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P
• heritable pulmonary arterial hypertension

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000235427 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.196-8531G>A		intron_variant	Intron 2 of 2	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.103-8531G>A		intron_variant	Intron 2 of 2		NP_001166366.1
CAV1	NM_001172896.2	c.103-8531G>A		intron_variant	Intron 1 of 1		NP_001166367.1
CAV1	NM_001172897.2	c.103-8531G>A		intron_variant	Intron 2 of 2		NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.196-8531G>A		intron_variant	Intron 2 of 2	1	NM_001753.5	ENSP00000339191.2

Frequencies

GnomAD3 genomes AF: 0.0728 AC: 11068 AN: 151974 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0728 AC: 11067 AN: 152092 Hom.: 657 Cov.: 32 AF XY: 0.0789 AC XY: 5863 AN XY: 74314

African (AFR) AF: 0.0177 AC: 734 AN: 41530

American (AMR) AF: 0.0831 AC: 1271 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1082 AN: 5156

South Asian (SAS) AF: 0.126 AC: 608 AN: 4810

European-Finnish (FIN) AF: 0.184 AC: 1936 AN: 10540

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5141 AN: 67980

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0648 Hom.: 48

Bravo AF: 0.0647

Asia WGS AF: 0.136 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		-0.050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3801994; hg19: chr7-116190469;