17-42403096-A-C

Variant names:

• chr17-42403096-A-C
• rs4796582
• NM_012232.6:c.*1591T>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.*1591T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,238 control chromosomes in the GnomAD database, including 54,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54650 hom., cov: 31)
  • Exomes 𝑓: 0.96 (54 hom.)
• Consequence: CAVIN1 NM_012232.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30

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=-1.02).
• BP6: Variant 17-42403096-A-C is Benign according to our data. Variant chr17-42403096-A-C is described in ClinVar as [Benign]. Clinvar id is 323260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6	c.*1591T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000357037.6	NP_036364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037	c.*1591T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_012232.6	ENSP00000349541.4

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127420 AN: 152002 Hom.: 54613 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.867

GnomAD4 exome AF: 0.958 AC: 113 AN: 118 Hom.: 54 Cov.: 0 AF XY: 0.950 AC XY: 76 AN XY: 80

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.948

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.838 AC: 127509 AN: 152120 Hom.: 54650 Cov.: 31 AF XY: 0.841 AC XY: 62583 AN XY: 74392

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.950

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.868

Alfa AF: 0.889 Hom.: 10441

Bravo AF: 0.829

Asia WGS AF: 0.957 AC: 3326 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital generalized lipodystrophy type 4 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-1.0
CADD	Benign	2.3
DANN	Benign	0.28

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: rs4796582; hg19: chr17-40555114;