7-116527154-C-T

Variant names:

• chr7-116527154-C-T
• rs926198
• NM_001753.5:c.195+465C>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+465C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 202,494 control chromosomes in the GnomAD database, including 44,719 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 (32735 hom., cov: 31)
  • Exomes 𝑓: 0.67 (11984 hom.)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 39 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.195+465C>T		intron_variant	Intron 2 of 2	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.102+465C>T		intron_variant	Intron 2 of 2		NP_001166366.1
CAV1	NM_001172896.2	c.102+465C>T		intron_variant	Intron 1 of 1		NP_001166367.1
CAV1	NM_001172897.2	c.102+465C>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.195+465C>T		intron_variant	Intron 2 of 2	1	NM_001753.5	ENSP00000339191.2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98430 AN: 151896 Hom.: 32713 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.673 AC: 33963 AN: 50480 Hom.: 11984 AF XY: 0.676 AC XY: 17410 AN XY: 25762

African (AFR) AF: 0.494 AC: 1026 AN: 2076

American (AMR) AF: 0.753 AC: 2692 AN: 3576

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 696 AN: 1170

East Asian (EAS) AF: 0.941 AC: 2895 AN: 3078

South Asian (SAS) AF: 0.650 AC: 3591 AN: 5526

European-Finnish (FIN) AF: 0.789 AC: 1499 AN: 1900

Middle Eastern (MID) AF: 0.588 AC: 127 AN: 216

European-Non Finnish (NFE) AF: 0.649 AC: 19558 AN: 30132

Other (OTH) AF: 0.670 AC: 1879 AN: 2806

GnomAD4 genome AF: 0.648 AC: 98499 AN: 152014 Hom.: 32735 Cov.: 31 AF XY: 0.656 AC XY: 48761 AN XY: 74298

African (AFR) AF: 0.520 AC: 21536 AN: 41428

American (AMR) AF: 0.705 AC: 10764 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.936 AC: 4845 AN: 5174

South Asian (SAS) AF: 0.688 AC: 3311 AN: 4810

European-Finnish (FIN) AF: 0.810 AC: 8556 AN: 10564

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45278 AN: 67986

Other (OTH) AF: 0.645 AC: 1362 AN: 2112

Alfa AF: 0.656 Hom.: 53073

Bravo AF: 0.635

Asia WGS AF: 0.797 AC: 2770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.66
PhyloP100		-0.23
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: rs926198; hg19: chr7-116167208;