rs963986

Variant names:

• chr17-42409561-G-C
• rs963986
• NM_012232.6:c.472-4173C>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.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
• Publications: 21 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):

• congenital generalized lipodystrophy type 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.93).
• 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 rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6	c.472-4173C>G		intron_variant	Intron 1 of 1	ENST00000357037.6	NP_036364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6	c.472-4173C>G		intron_variant	Intron 1 of 1	1	NM_012232.6	ENSP00000349541.4

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

African (AFR) AF: 0.115 AC: 4780 AN: 41492

American (AMR) AF: 0.129 AC: 1969 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1910 AN: 5148

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10257 AN: 67980

Other (OTH) AF: 0.156 AC: 330 AN: 2112

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
PhyloP100		-0.038
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: rs963986; hg19: chr17-40561579;