rs1049314

Variant names:

• chr7-116559641-C-A
• rs1049314
• NM_001753.5:c.*354C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*354C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*354C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001166366.1
CAV1	NM_001172896.2	c.*354C>A		3_prime_UTR_variant	Exon 2 of 2		NP_001166367.1
CAV1	NM_001172897.2	c.*354C>A		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.*354C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001753.5	ENSP00000339191.2

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

African (AFR) AF: 0.278 AC: 2582 AN: 9282

American (AMR) AF: 0.126 AC: 1493 AN: 11812

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 2635 AN: 12120

East Asian (EAS) AF: 0.00267 AC: 74 AN: 27700

South Asian (SAS) AF: 0.130 AC: 3462 AN: 26646

European-Finnish (FIN) AF: 0.0979 AC: 2710 AN: 27670

Middle Eastern (MID) AF: 0.187 AC: 329 AN: 1760

European-Non Finnish (NFE) AF: 0.163 AC: 38742 AN: 237060

Other (OTH) AF: 0.165 AC: 3743 AN: 22746

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

African (AFR) AF: 0.297 AC: 12180 AN: 40966

American (AMR) AF: 0.141 AC: 2127 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 739 AN: 3460

East Asian (EAS) AF: 0.0102 AC: 52 AN: 5106

South Asian (SAS) AF: 0.156 AC: 742 AN: 4744

European-Finnish (FIN) AF: 0.0988 AC: 964 AN: 9754

Middle Eastern (MID) AF: 0.221 AC: 64 AN: 290

European-Non Finnish (NFE) AF: 0.168 AC: 11355 AN: 67484

Other (OTH) AF: 0.199 AC: 416 AN: 2086

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
PhyloP100		-0.95
Mutation Taster		=100/0	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: rs1049314; hg19: chr7-116199695;