rs1049314

Positions:

• chr7-116559641-C-A
• chr7-116559641-C-T

Variant summary

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

The NM_001753.5(CAV1):​c.*354C>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 0.161 in 526,654 control chromosomes in the GnomAD database, including 8,027 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 (3181 hom., cov: 31)
  • Exomes 𝑓: 0.15 (4846 hom.)
• Consequence: CAV1 NM_001753.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*354C>A		3_prime_UTR_variant	3/3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*354C>A		3_prime_UTR_variant	3/3		NP_001166366.1
CAV1	NM_001172896.2	c.*354C>A		3_prime_UTR_variant	2/2		NP_001166367.1
CAV1	NM_001172897.2	c.*354C>A		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.*354C>A		3_prime_UTR_variant	3/3	1	NM_001753.5	ENSP00000339191	P3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 28816 AN: 149762 Hom.: 3178 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.148 AC: 55770 AN: 376796 Hom.: 4846 Cov.: 0 AF XY: 0.148 AC XY: 29010 AN XY: 196480

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.00267

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0979

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.193 AC: 28854 AN: 149858 Hom.: 3181 Cov.: 31 AF XY: 0.186 AC XY: 13579 AN XY: 73044

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0988

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.199

Alfa AF: 0.177 Hom.: 591

Bravo AF: 0.198

Asia WGS AF: 0.0880 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.40

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: rs1049314; hg19: chr7-116199695;