rs9252

Positions:

• chr17-42402831-G-A

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.*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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.237

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=-0.82).
• 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	UniProt
CAVIN1	NM_012232.6	c.*1856C>T		3_prime_UTR_variant	2/2	ENST00000357037.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAVIN1	ENST00000357037.6	c.*1856C>T		3_prime_UTR_variant	2/2	1	NM_012232.6	P1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10514 AN: 152066 Hom.: 506 Cov.: 31

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: 16 AN: 234 Hom.: 0 Cov.: 0 AF XY: 0.0843 AC XY: 14 AN XY: 166

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.: 31 AF XY: 0.0714 AC XY: 5314 AN XY: 74392

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

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	12
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

Other links and lift over

dbSNP: rs9252; hg19: chr17-40554849;