Variant 17-42402938-A-G 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.*1749T>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 0.845 in 152,140 control chromosomes in the GnomAD database, including 55,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55286 hom., cov: 30)

Exomes 𝑓: 0.92 ( 44 hom. )

Consequence

CAVIN1
NM_012232.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.538

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-42402938-A-G is Benign according to our data. Variant chr17-42402938-A-G is described in ClinVar as [Benign]. Clinvar id is 323258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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.*1749T>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
CAVIN1	ENST00000357037.6 linkuse as main transcript	c.*1749T>C		3_prime_UTR_variant	2/2	1	NM_012232.6	ENSP00000349541	P1	Q6NZI2-1

Frequencies

GnomAD3 genomes

AF:

0.845

AC:

128383

AN:

151918

Hom.:

55251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.925

Gnomad AMR

AF:

0.919

Gnomad ASJ

AF:

0.950

Gnomad EAS

AF:

0.989

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.898

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.908

Gnomad OTH

AF:

0.872

GnomAD4 exome

AF:

0.923

AC:

AN:

104

Hom.:

Cov.:

AF XY:

0.938

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.875

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.934

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.845

AC:

128471

AN:

152036

Hom.:

55286

Cov.:

AF XY:

0.848

AC XY:

63026

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.658

Gnomad4 AMR

AF:

0.918

Gnomad4 ASJ

AF:

0.950

Gnomad4 EAS

AF:

0.989

Gnomad4 SAS

AF:

0.953

Gnomad4 FIN

AF:

0.898

Gnomad4 NFE

AF:

0.908

Gnomad4 OTH

AF:

0.873

Alfa

AF:

0.879

Hom.:

10153

Bravo

AF:

0.837

Asia WGS

AF:

0.956

AC:

3325

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital generalized lipodystrophy type 4

Benign:1

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.42

DANN

Benign

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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