NM_012232.6:c.553_570dupGAGCTGGGCGAGGGCGAG

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_012232.6(CAVIN1):c.553_570dupGAGCTGGGCGAGGGCGAG(p.Glu190_Arg191insGluLeuGlyGluGlyGlu) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,612,404 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CAVIN1
NM_012232.6 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3B:1

Conservation

PhyloP100: 2.02

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00114 (173/152240) while in subpopulation AFR AF= 0.0039 (162/41552). AF 95% confidence interval is 0.00341. There are 1 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6 link	c.553_570dupGAGCTGGGCGAGGGCGAG	p.Glu190_Arg191insGluLeuGlyGluGlyGlu	conservative_inframe_insertion	Exon 2 of 2	ENST00000357037.6	NP_036364.2	Q6NZI2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6 link	c.553_570dupGAGCTGGGCGAGGGCGAG	p.Glu190_Arg191insGluLeuGlyGluGlyGlu	conservative_inframe_insertion	Exon 2 of 2	1	NM_012232.6	ENSP00000349541.4		Q6NZI2-1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000254

AC:

AN:

247982

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000145

AC:

211

AN:

1460164

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.00511

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00114

AC:

173

AN:

152240

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000528

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

See cases

Uncertain:1

Jan 09, 2023

Institute of Human Genetics, University Hospital Muenster

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ACMG categories: PM2,PM4 -

Monogenic diabetes

Uncertain:1

Feb 12, 2016

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria: PM4 -

not provided

Uncertain:1

Aug 07, 2023

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CAVIN1-related disorder

Benign:1

Jun 15, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over