17-42402899-G-C

Variant names:

• chr17-42402899-G-C
• rs11546699
• NM_012232.6:c.*1788C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012232.6(CAVIN1):​c.*1788C>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 0.0396 in 152,202 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (137 hom., cov: 31)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: CAVIN1 NM_012232.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0440

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-42402899-G-C is Benign according to our data. Variant chr17-42402899-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 323257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6	c.*1788C>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.*1788C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_012232.6	ENSP00000349541.4

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5986 AN: 151952 Hom.: 132 Cov.: 31

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0455 AC: 6 AN: 132 Hom.: 0 Cov.: 0 AF XY: 0.0568 AC XY: 5 AN XY: 88

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0396 AC: 6020 AN: 152070 Hom.: 137 Cov.: 31 AF XY: 0.0408 AC XY: 3036 AN XY: 74344

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.0192

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0116 Hom.: 3

Bravo AF: 0.0364

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital generalized lipodystrophy type 4 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 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	-0.85
CADD	Benign	6.3
DANN	Benign	0.58
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: rs11546699; hg19: chr17-40554917;