17-42414633-T-C

Position:

• chr17-42414633-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAVIN1	NM_012232.6	c.471+7994A>G		intron_variant		ENST00000357037.6	NP_036364.2
CAVIN1	XM_005257242.5	c.472-2383A>G		intron_variant			XP_005257299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6	c.471+7994A>G		intron_variant		1	NM_012232.6	ENSP00000349541.4

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

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.793

Alfa AF: 0.781 Hom.: 58007

Bravo AF: 0.778

Asia WGS AF: 0.799 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.9
DANN	Benign	0.56

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: rs8070945; hg19: chr17-40566651;