rs9920

Variant names:

• chr7-116560038-T-C
• rs9920
• NM_001753.5:c.*751T>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.*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
• Publications: 42 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=-0.89).
• 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 rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*751T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*751T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001166366.1
CAV1	NM_001172896.2	c.*751T>C		3_prime_UTR_variant	Exon 2 of 2		NP_001166367.1
CAV1	NM_001172897.2	c.*751T>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.*751T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001753.5	ENSP00000339191.2
CAV1	ENST00000393467.1	c.*751T>C		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000377110.1
CAV1	ENST00000405348.6	c.*751T>C		3_prime_UTR_variant	Exon 3 of 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

African (AFR) AF: 0.0227 AC: 159 AN: 6994

American (AMR) AF: 0.0651 AC: 473 AN: 7266

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 951 AN: 9028

East Asian (EAS) AF: 0.00 AC: 0 AN: 22588

South Asian (SAS) AF: 0.0499 AC: 106 AN: 2126

European-Finnish (FIN) AF: 0.0739 AC: 1525 AN: 20642

Middle Eastern (MID) AF: 0.0680 AC: 86 AN: 1264

European-Non Finnish (NFE) AF: 0.101 AC: 15559 AN: 154390

Other (OTH) AF: 0.0825 AC: 1319 AN: 15986

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

African (AFR) AF: 0.0191 AC: 792 AN: 41534

American (AMR) AF: 0.0626 AC: 957 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0568 AC: 274 AN: 4820

European-Finnish (FIN) AF: 0.0696 AC: 737 AN: 10594

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0978 AC: 6651 AN: 67992

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0911 Hom.: 2177

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
PhyloP100		-0.15
Mutation Taster		=97/3	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: rs9920; hg19: chr7-116200092;