17-42403241-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012232.6(CAVIN1):​c.*1446G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,462 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 225 hom., cov: 31)
Exomes 𝑓: 0.076 ( 0 hom. )

Consequence

CAVIN1
NM_012232.6 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.39
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 17-42403241-C-G is Benign according to our data. Variant chr17-42403241-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 323263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CAVIN1NM_012232.6 linkuse as main transcriptc.*1446G>C 3_prime_UTR_variant 2/2 ENST00000357037.6 NP_036364.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAVIN1ENST00000357037.6 linkuse as main transcriptc.*1446G>C 3_prime_UTR_variant 2/21 NM_012232.6 ENSP00000349541 P1Q6NZI2-1

Frequencies

GnomAD3 genomes
AF:
0.0446
AC:
6787
AN:
152028
Hom.:
225
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0124
Gnomad AMI
AF:
0.102
Gnomad AMR
AF:
0.0721
Gnomad ASJ
AF:
0.0609
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.0110
Gnomad FIN
AF:
0.0195
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0653
Gnomad OTH
AF:
0.0729
GnomAD4 exome
AF:
0.0759
AC:
24
AN:
316
Hom.:
0
Cov.:
0
AF XY:
0.0748
AC XY:
16
AN XY:
214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0741
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0500
Gnomad4 NFE exome
AF:
0.0903
Gnomad4 OTH exome
AF:
0.100
GnomAD4 genome
AF:
0.0446
AC:
6787
AN:
152146
Hom.:
225
Cov.:
31
AF XY:
0.0429
AC XY:
3189
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0124
Gnomad4 AMR
AF:
0.0721
Gnomad4 ASJ
AF:
0.0609
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.0108
Gnomad4 FIN
AF:
0.0195
Gnomad4 NFE
AF:
0.0653
Gnomad4 OTH
AF:
0.0721
Alfa
AF:
0.0515
Hom.:
35
Bravo
AF:
0.0479
Asia WGS
AF:
0.00837
AC:
29
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Congenital generalized lipodystrophy type 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
8.5
DANN
Benign
0.67
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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

LitVar

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

Other links and lift over

dbSNP: rs4796583; hg19: chr17-40555259; API