7-116549129-T-C

Variant names:

• chr7-116549129-T-C
• rs3779514
• NM_001753.5:c.196-9817T>C

Variant summary

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

The NM_001753.5(CAV1):​c.196-9817T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,138 control chromosomes in the GnomAD database, including 51,960 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 0.83 (51960 hom., cov: 31)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.37
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV1	NM_001753.5	MANE Select	c.196-9817T>C		intron	N/A	NP_001744.2
	CAV1	NM_001172895.1		c.103-9817T>C		intron	N/A	NP_001166366.1
	CAV1	NM_001172896.2		c.103-9817T>C		intron	N/A	NP_001166367.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV1	ENST00000341049.7	TSL:1 MANE Select	c.196-9817T>C		intron	N/A	ENSP00000339191.2
	CAV1	ENST00000393467.1	TSL:1	c.103-9817T>C		intron	N/A	ENSP00000377110.1
	CAV1	ENST00000393468.1	TSL:1	c.103-9817T>C		intron	N/A	ENSP00000377111.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125440 AN: 152020 Hom.: 51919 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.825 AC: 125539 AN: 152138 Hom.: 51960 Cov.: 31 AF XY: 0.827 AC XY: 61520 AN XY: 74384

African (AFR) AF: 0.762 AC: 31621 AN: 41474

American (AMR) AF: 0.857 AC: 13102 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2997 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4898 AN: 5174

South Asian (SAS) AF: 0.865 AC: 4170 AN: 4820

European-Finnish (FIN) AF: 0.853 AC: 9032 AN: 10592

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57041 AN: 68000

Other (OTH) AF: 0.822 AC: 1732 AN: 2108

Alfa AF: 0.833 Hom.: 34308

Bravo AF: 0.823

Asia WGS AF: 0.885 AC: 3079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.46
PhyloP100		-4.4
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: rs3779514; hg19: chr7-116189183;