rs4730748

Variant names:

• chr7-116527541-A-G
• rs4730748
• NM_001753.5:c.195+852A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-116527541-A-G
• chr7-116527541-A-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.195+852A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,216 control chromosomes in the GnomAD database, including 2,436 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 0.17 (2436 hom., cov: 33)
• Consequence: CAV1 NM_001753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV1	NM_001753.5	c.195+852A>G		intron_variant	Intron 2 of 2	ENST00000341049.7	NP_001744.2
CAV1	NM_001172895.1	c.102+852A>G		intron_variant	Intron 2 of 2		NP_001166366.1
CAV1	NM_001172896.2	c.102+852A>G		intron_variant	Intron 1 of 1		NP_001166367.1
CAV1	NM_001172897.2	c.102+852A>G		intron_variant	Intron 2 of 2		NP_001166368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV1	ENST00000341049.7	c.195+852A>G		intron_variant	Intron 2 of 2	1	NM_001753.5	ENSP00000339191.2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26047 AN: 152098 Hom.: 2439 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 26048 AN: 152216 Hom.: 2436 Cov.: 33 AF XY: 0.165 AC XY: 12308 AN XY: 74432

African (AFR) AF: 0.202 AC: 8388 AN: 41498

American (AMR) AF: 0.153 AC: 2334 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3468

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5190

South Asian (SAS) AF: 0.177 AC: 852 AN: 4820

European-Finnish (FIN) AF: 0.0694 AC: 736 AN: 10612

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12124 AN: 68012

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.0874 Hom.: 108

Bravo AF: 0.179

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.69
PhyloP100		0.27
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: rs4730748; hg19: chr7-116167595;