17-42414633-T-C

Variant names:

• chr17-42414633-T-C
• rs8070945
• NM_012232.6:c.471+7994A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012232.6(CAVIN1):​c.471+7994A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 151,882 control chromosomes in the GnomAD database, including 45,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45630 hom., cov: 29)
• Consequence: CAVIN1 NM_012232.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 8 publications found

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]

CAVIN1 Gene-Disease associations (from GenCC):

• lipodystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital generalized lipodystrophy type 4

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012232.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN1	NM_012232.6	MANE Select	c.471+7994A>G		intron	N/A	NP_036364.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN1	ENST00000357037.6	TSL:1 MANE Select	c.471+7994A>G		intron	N/A	ENSP00000349541.4	Q6NZI2-1
	CAVIN1	ENST00000944723.1		c.318+8147A>G		intron	N/A	ENSP00000614782.1
	CAVIN1	ENST00000944722.1		c.417+8048A>G		intron	N/A	ENSP00000614781.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117443 AN: 151764 Hom.: 45576 Cov.: 29

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.792

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.774 AC: 117556 AN: 151882 Hom.: 45630 Cov.: 29 AF XY: 0.774 AC XY: 57415 AN XY: 74224

African (AFR) AF: 0.720 AC: 29772 AN: 41364

American (AMR) AF: 0.851 AC: 12981 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2913 AN: 3468

East Asian (EAS) AF: 0.869 AC: 4483 AN: 5156

South Asian (SAS) AF: 0.736 AC: 3529 AN: 4792

European-Finnish (FIN) AF: 0.775 AC: 8186 AN: 10566

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53072 AN: 67970

Other (OTH) AF: 0.793 AC: 1670 AN: 2106

Alfa AF: 0.781 Hom.: 81401

Bravo AF: 0.778

Asia WGS AF: 0.799 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.9
DANN	Benign	0.56
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8070945; hg19: chr17-40566651;