rs963986

chr17-42409561-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012232.6(CAVIN1):c.472-4173C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,078 control chromosomes in the GnomAD database, including 1,939 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 0.15 (1939 hom., cov: 31)
• Consequence: CAVIN1 NM_012232.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAVIN1	NM_012232.6	c.472-4173C>G		intron_variant		ENST00000357037.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAVIN1	ENST00000357037.6	c.472-4173C>G		intron_variant		1	NM_012232.6	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22713 AN: 151960 Hom.: 1934 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.149 AC: 22732 AN: 152078 Hom.: 1939 Cov.: 31 AF XY: 0.153 AC XY: 11396 AN XY: 74326

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.156

Alfa AF: 0.144 Hom.: 237

Bravo AF: 0.145

Asia WGS AF: 0.320 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.8
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: rs963986; hg19: chr17-40561579;