Variant 17-42402831-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012232.6(CAVIN1):c.*1856C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,418 control chromosomes in the GnomAD database, including 506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 506 hom., cov: 31)

Exomes 𝑓: 0.068 ( 0 hom. )

Consequence

CAVIN1
NM_012232.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.237

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-42402831-G-A is Benign according to our data. Variant chr17-42402831-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 323256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAVIN1	NM_012232.6 linkuse as main transcript	c.*1856C>T		3_prime_UTR_variant	2/2	ENST00000357037.6	NP_036364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6 linkuse as main transcript	c.*1856C>T		3_prime_UTR_variant	2/2	1	NM_012232.6	ENSP00000349541	P1	Q6NZI2-1

Frequencies

GnomAD3 genomes

AF:

0.0691

AC:

10514

AN:

152066

Hom.:

506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0621

Gnomad ASJ

AF:

0.0857

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.0762

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0872

Gnomad OTH

AF:

0.0851

GnomAD4 exome

AF:

0.0684

AC:

AN:

234

Hom.:

Cov.:

AF XY:

0.0843

AC XY:

AN XY:

166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0761

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0763

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0691

AC:

10515

AN:

152184

Hom.:

506

Cov.:

AF XY:

0.0714

AC XY:

5314

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0182

Gnomad4 AMR

AF:

0.0620

Gnomad4 ASJ

AF:

0.0857

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.0762

Gnomad4 NFE

AF:

0.0872

Gnomad4 OTH

AF:

0.0851

Alfa

AF:

0.0859

Hom.:

403

Bravo

AF:

0.0649

Asia WGS

AF:

0.138

AC:

478

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 submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital generalized lipodystrophy type 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This 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

-0.82

CADD

Benign

DANN

Benign

0.58

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.

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