NM_001753.5:c.195+13091G>A

Variant names:

• chr7-116539780-G-A
• rs3807987
• NM_001753.5:c.195+13091G>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+13091G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,136 control chromosomes in the GnomAD database, including 638 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 0.078 (638 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 37 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.195+13091G>A		intron_variant	Intron 2 of 2	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.102+13091G>A		intron_variant	Intron 2 of 2		NP_001166366.1
CAV1	NM_001172896.2	c.102+13091G>A		intron_variant	Intron 1 of 1		NP_001166367.1
CAV1	NM_001172897.2	c.102+13091G>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+13091G>A		intron_variant	Intron 2 of 2	1	NM_001753.5	ENSP00000339191.2

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11804 AN: 152018 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0776 AC: 11806 AN: 152136 Hom.: 638 Cov.: 32 AF XY: 0.0831 AC XY: 6183 AN XY: 74384

African (AFR) AF: 0.0495 AC: 2055 AN: 41510

American (AMR) AF: 0.0847 AC: 1295 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.165 AC: 853 AN: 5164

South Asian (SAS) AF: 0.118 AC: 567 AN: 4816

European-Finnish (FIN) AF: 0.175 AC: 1851 AN: 10578

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0723 AC: 4918 AN: 67990

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0682 Hom.: 71

Bravo AF: 0.0711

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		-1.2
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: rs3807987; hg19: chr7-116179834;