NM_001753.5:c.195+701A>T

Variant names:

• chr7-116527390-A-T
• rs917664
• NM_001753.5:c.195+701A>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.195+701A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,058 control chromosomes in the GnomAD database, including 32,736 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 0.65 (32736 hom., cov: 32)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 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.195+701A>T		intron	N/A	NP_001744.2
	CAV1	NM_001172895.1		c.102+701A>T		intron	N/A	NP_001166366.1
	CAV1	NM_001172896.2		c.102+701A>T		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.195+701A>T		intron	N/A	ENSP00000339191.2
	CAV1	ENST00000393467.1	TSL:1	c.102+701A>T		intron	N/A	ENSP00000377110.1
	CAV1	ENST00000393468.1	TSL:1	c.102+701A>T		intron	N/A	ENSP00000377111.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98433 AN: 151940 Hom.: 32714 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.648 AC: 98502 AN: 152058 Hom.: 32736 Cov.: 32 AF XY: 0.656 AC XY: 48770 AN XY: 74342

African (AFR) AF: 0.520 AC: 21538 AN: 41452

American (AMR) AF: 0.705 AC: 10770 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2141 AN: 3470

East Asian (EAS) AF: 0.936 AC: 4856 AN: 5186

South Asian (SAS) AF: 0.688 AC: 3307 AN: 4810

European-Finnish (FIN) AF: 0.809 AC: 8563 AN: 10580

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45266 AN: 67970

Other (OTH) AF: 0.645 AC: 1354 AN: 2100

Alfa AF: 0.658 Hom.: 4114

Bravo AF: 0.635

Asia WGS AF: 0.797 AC: 2770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.84
DANN	Benign	0.62
PhyloP100		-1.1
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: rs917664; hg19: chr7-116167444;