7-116560038-T-C

Position:

• chr7-116560038-T-C

Variant summary

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

The NM_001753.5(CAV1):​c.*751T>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 0.0771 in 392,480 control chromosomes in the GnomAD database, including 1,438 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 0.066 (464 hom., cov: 32)
  • Exomes 𝑓: 0.084 (974 hom.)
• Consequence: CAV1 NM_001753.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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 (NFE) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*751T>C		3_prime_UTR_variant	3/3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*751T>C		3_prime_UTR_variant	3/3		NP_001166366.1
CAV1	NM_001172896.2	c.*751T>C		3_prime_UTR_variant	2/2		NP_001166367.1
CAV1	NM_001172897.2	c.*751T>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.*751T>C		3_prime_UTR_variant	3/3	1	NM_001753.5	ENSP00000339191.2
CAV1	ENST00000393467.1	c.*751T>C		3_prime_UTR_variant	2/2	1		ENSP00000377110.1
CAV1	ENST00000405348.6	c.*751T>C		3_prime_UTR_variant	3/3	5		ENSP00000384348.1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10099 AN: 152078 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.0895

GnomAD4 exome AF: 0.0840 AC: 20178 AN: 240284 Hom.: 974 Cov.: 0 AF XY: 0.0848 AC XY: 10345 AN XY: 121932

Gnomad4 AFR exome AF: 0.0227

Gnomad4 AMR exome AF: 0.0651

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0499

Gnomad4 FIN exome AF: 0.0739

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0825

GnomAD4 genome AF: 0.0663 AC: 10094 AN: 152196 Hom.: 464 Cov.: 32 AF XY: 0.0641 AC XY: 4767 AN XY: 74408

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0626

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0568

Gnomad4 FIN AF: 0.0696

Gnomad4 NFE AF: 0.0978

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0970 Hom.: 1093

Bravo AF: 0.0653

Asia WGS AF: 0.0200 AC: 71 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	0.47
DANN	Benign	0.47

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: rs9920; hg19: chr7-116200092;