rs7804372

Variant names:

• chr7-116554174-T-A
• rs7804372
• NM_001753.5:c.196-4772T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-116554174-T-A
• chr7-116554174-T-G

Variant summary

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

The NM_001753.5(CAV1):​c.196-4772T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,110 control chromosomes in the GnomAD database, including 5,465 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 0.26 (5465 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 46 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 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.196-4772T>A		intron	N/A	NP_001744.2
	CAV1	NM_001172895.1		c.103-4772T>A		intron	N/A	NP_001166366.1
	CAV1	NM_001172896.2		c.103-4772T>A		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.196-4772T>A		intron	N/A	ENSP00000339191.2
	CAV1	ENST00000393467.1	TSL:1	c.103-4772T>A		intron	N/A	ENSP00000377110.1
	CAV1	ENST00000393468.1	TSL:1	c.103-4772T>A		intron	N/A	ENSP00000377111.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40201 AN: 151992 Hom.: 5462 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.265 AC: 40237 AN: 152110 Hom.: 5465 Cov.: 32 AF XY: 0.264 AC XY: 19615 AN XY: 74370

African (AFR) AF: 0.319 AC: 13229 AN: 41468

American (AMR) AF: 0.224 AC: 3420 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 865 AN: 3466

East Asian (EAS) AF: 0.220 AC: 1138 AN: 5182

South Asian (SAS) AF: 0.260 AC: 1253 AN: 4822

European-Finnish (FIN) AF: 0.278 AC: 2939 AN: 10582

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16523 AN: 67988

Other (OTH) AF: 0.257 AC: 542 AN: 2112

Alfa AF: 0.246 Hom.: 604

Bravo AF: 0.264

Asia WGS AF: 0.214 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.57
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: rs7804372; hg19: chr7-116194228;