17-42403241-C-G

Position:

• chr17-42403241-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.39

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]

ACMG classification

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
CAVIN1	NM_012232.6	c.*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
CAVIN1	ENST00000357037.6	c.*1446G>C		3_prime_UTR_variant	2/2	1	NM_012232.6	ENSP00000349541	P1

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6787 AN: 152028 Hom.: 225 Cov.: 31

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

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

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

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	-0.79
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

Other links and lift over

dbSNP: rs4796583; hg19: chr17-40555259;