chr7-116550543-C-T

Variant names:

• chr7-116550543-C-T
• rs3801995
• NM_001753.5:c.196-8403C>T

Variant summary

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

The NM_001753.5(CAV1):​c.196-8403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,004 control chromosomes in the GnomAD database, including 6,451 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 (6451 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.196-8403C>T		intron_variant	Intron 2 of 2	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.103-8403C>T		intron_variant	Intron 2 of 2		NP_001166366.1
CAV1	NM_001172896.2	c.103-8403C>T		intron_variant	Intron 1 of 1		NP_001166367.1
CAV1	NM_001172897.2	c.103-8403C>T		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.196-8403C>T		intron_variant	Intron 2 of 2	1	NM_001753.5	ENSP00000339191.2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43029 AN: 151886 Hom.: 6444 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.283 AC: 43081 AN: 152004 Hom.: 6451 Cov.: 32 AF XY: 0.282 AC XY: 20976 AN XY: 74266

African (AFR) AF: 0.385 AC: 15941 AN: 41448

American (AMR) AF: 0.231 AC: 3526 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1133 AN: 5168

South Asian (SAS) AF: 0.261 AC: 1255 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2935 AN: 10550

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16538 AN: 67956

Other (OTH) AF: 0.266 AC: 561 AN: 2108

Alfa AF: 0.261 Hom.: 727

Bravo AF: 0.286

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	-0.85
CADD	Benign	0.98
DANN	Benign	0.24
PhyloP100		-0.44
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: rs3801995; hg19: chr7-116190597;