Genetic Variant CAVIN1:c.472-4346G>C (chr17-42409734-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012232.6(CAVIN1):c.472-4346G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,650 control chromosomes in the GnomAD database, including 27,990 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 0.58 ( 27990 hom., cov: 29)

Consequence

CAVIN1
NM_012232.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.04

Publications

7 publications found

Variant links:

Genes affected

CAVIN1 (HGNC:9688): (caveolae associated protein 1) This gene encodes a protein that enables the dissociation of paused ternary polymerase I transcription complexes from the 3' end of pre-rRNA transcripts. This protein regulates rRNA transcription by promoting the dissociation of transcription complexes and the reinitiation of polymerase I on nascent rRNA transcripts. This protein also localizes to caveolae at the plasma membrane and is thought to play a critical role in the formation of caveolae and the stabilization of caveolins. This protein translocates from caveolae to the cytoplasm after insulin stimulation. Caveolae contain truncated forms of this protein and may be the site of phosphorylation-dependent proteolysis. This protein is also thought to modify lipid metabolism and insulin-regulated gene expression. Mutations in this gene result in a disorder characterized by generalized lipodystrophy and muscular dystrophy. [provided by RefSeq, Nov 2009]

CAVIN1 Gene-Disease associations (from GenCC):

congenital generalized lipodystrophy type 4
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Berardinelli-Seip congenital lipodystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CAVIN1 links:

ENSG00000289579 (HGNC:58351):

ENSG00000289579 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6 link	c.472-4346G>C		intron_variant	Intron 1 of 1	ENST00000357037.6	NP_036364.2
CAVIN1	XM_005257242.5 link	c.*2310G>C		downstream_gene_variant			XP_005257299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6 link	c.472-4346G>C		intron_variant	Intron 1 of 1	1	NM_012232.6	ENSP00000349541.4
ENSG00000289579	ENST00000691590.1 link	n.*158G>C		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.584

AC:

88481

AN:

151532

Hom.:

27988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.719

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.627

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

GnomAD4 genome

AF:

0.584

AC:

88498

AN:

151650

Hom.:

27990

Cov.:

AF XY:

0.581

AC XY:

43007

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.327

AC:

13506

AN:

41324

American (AMR)

AF:

0.719

AC:

10950

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.777

AC:

2694

AN:

3468

East Asian (EAS)

AF:

0.589

AC:

3024

AN:

5134

South Asian (SAS)

AF:

0.535

AC:

2566

AN:

4798

European-Finnish (FIN)

AF:

0.640

AC:

6717

AN:

10488

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

46991

AN:

67904

Other (OTH)

AF:

0.620

AC:

1310

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1640

3281

4921

6562

8202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.462

Hom.:

1171

Bravo

AF:

0.582

Asia WGS

AF:

0.488

AC:

1697

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over