rs1049334

Variant names:

• chr7-116560326-G-A
• rs1049334
• NM_001753.5:c.*1039G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-116560326-G-A
• chr7-116560326-G-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.*1039G>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 0.0866 in 152,532 control chromosomes in the GnomAD database, including 727 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 0.087 (725 hom., cov: 32)
  • Exomes 𝑓: 0.085 (2 hom.)
• Consequence: CAV1 NM_001753.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 28 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.*1039G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.*1039G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001166366.1
CAV1	NM_001172896.2	c.*1039G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001166367.1
CAV1	NM_001172897.2	c.*1039G>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.*1039G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001753.5	ENSP00000339191.2
CAV1	ENST00000393467.1	c.*1039G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000377110.1
CAV1	ENST00000405348.6	c.*1039G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000384348.1

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13173 AN: 152016 Hom.: 725 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.0645

GnomAD4 exome AF: 0.0854 AC: 34 AN: 398 Hom.: 2 Cov.: 0 AF XY: 0.105 AC XY: 23 AN XY: 220

African (AFR) AF: 0.111 AC: 2 AN: 18

American (AMR) AF: 0.300 AC: 3 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16

East Asian (EAS) AF: 0.500 AC: 3 AN: 6

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0745 AC: 24 AN: 322

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.0866 AC: 13175 AN: 152134 Hom.: 725 Cov.: 32 AF XY: 0.0922 AC XY: 6860 AN XY: 74372

African (AFR) AF: 0.0684 AC: 2841 AN: 41526

American (AMR) AF: 0.0879 AC: 1343 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1083 AN: 5158

South Asian (SAS) AF: 0.106 AC: 510 AN: 4828

European-Finnish (FIN) AF: 0.183 AC: 1937 AN: 10568

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5150 AN: 67990

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0699 Hom.: 574

Bravo AF: 0.0812

Asia WGS AF: 0.133 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.7
DANN	Benign	0.82
PhyloP100		0.14
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: rs1049334; hg19: chr7-116200380;