17-42402983-G-C

Variant names:

• chr17-42402983-G-C
• rs7210713
• NM_012232.6:c.*1704C>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.*1704C>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 0.845 in 152,446 control chromosomes in the GnomAD database, including 55,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (55314 hom., cov: 32)
  • Exomes 𝑓: 0.94 (129 hom.)
• Consequence: CAVIN1 NM_012232.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.495

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=-0.91).
• BP6: Variant 17-42402983-G-C is Benign according to our data. Variant chr17-42402983-G-C is described in ClinVar as [Benign]. Clinvar id is 323259.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.*1704C>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.*1704C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_012232.6	ENSP00000349541.4

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128464 AN: 152036 Hom.: 55279 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.918

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: 0.872

GnomAD4 exome AF: 0.938 AC: 274 AN: 292 Hom.: 129 Cov.: 0 AF XY: 0.941 AC XY: 207 AN XY: 220

Gnomad4 AFR exome AF: 0.667

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.941

Gnomad4 OTH exome AF: 0.917

GnomAD4 genome AF: 0.845 AC: 128552 AN: 152154 Hom.: 55314 Cov.: 32 AF XY: 0.848 AC XY: 63057 AN XY: 74380

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.918

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: 0.873

Alfa AF: 0.849 Hom.: 2828

Bravo AF: 0.837

Asia WGS AF: 0.957 AC: 3327 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	-0.91
CADD	Benign	2.9
DANN	Benign	0.43

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: rs7210713; hg19: chr17-40555001;