7-116537771-G-A

Variant names:

• chr7-116537771-G-A
• rs3807986
• NM_001753.5:c.195+11082G>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.195+11082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,970 control chromosomes in the GnomAD database, including 35,799 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 0.67 (35799 hom., cov: 31)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 13 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

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 = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.195+11082G>A		intron_variant	Intron 2 of 2	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.102+11082G>A		intron_variant	Intron 2 of 2		NP_001166366.1
CAV1	NM_001172896.2	c.102+11082G>A		intron_variant	Intron 1 of 1		NP_001166367.1
CAV1	NM_001172897.2	c.102+11082G>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.195+11082G>A		intron_variant	Intron 2 of 2	1	NM_001753.5	ENSP00000339191.2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101655 AN: 151852 Hom.: 35788 Cov.: 31

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.669 AC: 101697 AN: 151970 Hom.: 35799 Cov.: 31 AF XY: 0.670 AC XY: 49737 AN XY: 74274

African (AFR) AF: 0.433 AC: 17948 AN: 41406

American (AMR) AF: 0.737 AC: 11257 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4031 AN: 5168

South Asian (SAS) AF: 0.745 AC: 3578 AN: 4804

European-Finnish (FIN) AF: 0.704 AC: 7433 AN: 10554

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52149 AN: 67986

Other (OTH) AF: 0.706 AC: 1485 AN: 2104

Alfa AF: 0.744 Hom.: 36888

Bravo AF: 0.660

Asia WGS AF: 0.752 AC: 2613 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	6.7
DANN	Benign	0.27
PhyloP100		1.9
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: rs3807986; hg19: chr7-116177825;