7-116526650-C-T

Variant names:

• chr7-116526650-C-T
• rs10029
• ENST00000614113.5:c.334C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000614113.5(CAV1):​c.334C>T​(p.Gln112*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,128 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q112Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.034 (295 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (223 hom.)
• Consequence: CAV1 ENST00000614113.5 stop_gained
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.02
• Publications: 3 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
• congenital generalized lipodystrophy type 3

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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
• lipodystrophy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-116526650-C-T is Benign according to our data. Variant chr7-116526650-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000614113.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV1	NM_001753.5	MANE Select	c.156C>T	p.Val52Val	synonymous	Exon 2 of 3	NP_001744.2
	CAV1	NM_001172895.1		c.63C>T	p.Val21Val	synonymous	Exon 2 of 3	NP_001166366.1	Q59E85
	CAV1	NM_001172896.2		c.63C>T	p.Val21Val	synonymous	Exon 1 of 2	NP_001166367.1	Q03135-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV1	ENST00000614113.5	TSL:1	c.334C>T	p.Gln112*	stop_gained	Exon 3 of 4	ENSP00000479447.2	A0A7P0YWJ6
	CAV1	ENST00000341049.7	TSL:1 MANE Select	c.156C>T	p.Val52Val	synonymous	Exon 2 of 3	ENSP00000339191.2	Q03135-1
	CAV1	ENST00000393467.1	TSL:1	c.63C>T	p.Val21Val	synonymous	Exon 1 of 2	ENSP00000377110.1	Q03135-2

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5184 AN: 152160 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.00890 AC: 2238 AN: 251354 AF XY: 0.00651

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00700

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00345 AC: 5037 AN: 1461850 Hom.: 223 Cov.: 32 AF XY: 0.00292 AC XY: 2123 AN XY: 727220

African (AFR) AF: 0.118 AC: 3954 AN: 33480

American (AMR) AF: 0.00751 AC: 336 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86244

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53398

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5768

European-Non Finnish (NFE) AF: 0.000201 AC: 224 AN: 1112004

Other (OTH) AF: 0.00752 AC: 454 AN: 60396

GnomAD4 genome AF: 0.0341 AC: 5195 AN: 152278 Hom.: 295 Cov.: 32 AF XY: 0.0327 AC XY: 2435 AN XY: 74470

African (AFR) AF: 0.116 AC: 4825 AN: 41554

American (AMR) AF: 0.0184 AC: 281 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68022

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0150 Hom.: 99

Bravo AF: 0.0384

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Pulmonary hypertension, primary, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		1.0
PromoterAI		-0.090	Neutral
Mutation Taster		=18/82	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: rs10029; hg19: chr7-116166704;