rs8713

Positions:

• chr7-116559743-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001753.5(CAV1):​c.*456A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 433,510 control chromosomes in the GnomAD database, including 6,984 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 0.19 (3204 hom., cov: 32)
  • Exomes 𝑓: 0.15 (3780 hom.)
• Consequence: CAV1 NM_001753.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*456A>C		3_prime_UTR_variant	3/3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*456A>C		3_prime_UTR_variant	3/3		NP_001166366.1
CAV1	NM_001172896.2	c.*456A>C		3_prime_UTR_variant	2/2		NP_001166367.1
CAV1	NM_001172897.2	c.*456A>C		3_prime_UTR_variant	3/3		NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.*456A>C		3_prime_UTR_variant	3/3	1	NM_001753.5	ENSP00000339191	P3
CAV1	ENST00000393467.1	c.*456A>C		3_prime_UTR_variant	2/2	1		ENSP00000377110	A1
CAV1	ENST00000405348.6	c.*456A>C		3_prime_UTR_variant	3/3	5		ENSP00000384348	A1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28979 AN: 151920 Hom.: 3201 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.152 AC: 42644 AN: 281472 Hom.: 3780 Cov.: 0 AF XY: 0.152 AC XY: 21847 AN XY: 143542

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.00222

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0999

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.191 AC: 29019 AN: 152038 Hom.: 3204 Cov.: 32 AF XY: 0.184 AC XY: 13676 AN XY: 74326

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.197

Alfa AF: 0.175 Hom.: 4425

Bravo AF: 0.198

Asia WGS AF: 0.0880 AC: 310 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs8713; hg19: chr7-116199797;