chr7-116559743-A-C

Variant names:

• chr7-116559743-A-C
• rs8713
• NM_001753.5:c.*456A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital generalized lipodystrophy type 3

  Inheritance: AD, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P
• 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*456A>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*456A>C		3_prime_UTR_variant	Exon 3 of 3		NP_001166366.1
CAV1	NM_001172896.2	c.*456A>C		3_prime_UTR_variant	Exon 2 of 2		NP_001166367.1
CAV1	NM_001172897.2	c.*456A>C		3_prime_UTR_variant	Exon 3 of 3		NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.*456A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001753.5	ENSP00000339191.2

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

African (AFR) AF: 0.286 AC: 2119 AN: 7408

American (AMR) AF: 0.127 AC: 1302 AN: 10244

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 2223 AN: 9852

East Asian (EAS) AF: 0.00222 AC: 54 AN: 24352

South Asian (SAS) AF: 0.142 AC: 1063 AN: 7494

European-Finnish (FIN) AF: 0.0999 AC: 2270 AN: 22720

Middle Eastern (MID) AF: 0.182 AC: 254 AN: 1394

European-Non Finnish (NFE) AF: 0.168 AC: 30283 AN: 179894

Other (OTH) AF: 0.170 AC: 3076 AN: 18114

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

African (AFR) AF: 0.295 AC: 12242 AN: 41448

American (AMR) AF: 0.140 AC: 2139 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3468

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5178

South Asian (SAS) AF: 0.155 AC: 749 AN: 4820

European-Finnish (FIN) AF: 0.0954 AC: 1007 AN: 10560

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11397 AN: 67974

Other (OTH) AF: 0.197 AC: 415 AN: 2106

Alfa AF: 0.178 Hom.: 10224

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
PhyloP100		0.35
Mutation Taster		=99/1	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: rs8713; hg19: chr7-116199797;