7-116560469-G-A

Position:

• chr7-116560469-G-A

Variant summary

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

The NM_001753.5(CAV1):​c.*1182G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,102 control chromosomes in the GnomAD database, including 3,180 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 (3180 hom., cov: 32)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: CAV1 NM_001753.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV1	NM_001753.5	c.*1182G>A		3_prime_UTR_variant	3/3	ENST00000341049.7
CAV1	NM_001172895.1	c.*1182G>A		3_prime_UTR_variant	3/3
CAV1	NM_001172896.2	c.*1182G>A		3_prime_UTR_variant	2/2
CAV1	NM_001172897.2	c.*1182G>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV1	ENST00000341049.7	c.*1182G>A		3_prime_UTR_variant	3/3	1	NM_001753.5	P3
CAV1	ENST00000393467.1	c.*1182G>A		3_prime_UTR_variant	2/2	1		A1
CAV1	ENST00000405348.6	c.*1182G>A		3_prime_UTR_variant	3/3	5		A1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28891 AN: 151962 Hom.: 3178 Cov.: 32

Gnomad AFR AF: 0.293

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: 0.0951

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.0455 AC: 1 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.190 AC: 28930 AN: 152080 Hom.: 3180 Cov.: 32 AF XY: 0.183 AC XY: 13630 AN XY: 74366

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0101

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.197

Alfa AF: 0.171 Hom.: 1129

Bravo AF: 0.197

Asia WGS AF: 0.0880 AC: 309 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.72

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: rs6867; hg19: chr7-116200523;