chr17-42414732-C-G

Variant names:

• chr17-42414732-C-G
• rs2062213
• NM_012232.6:c.471+7895G>C

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+7895G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 152,110 control chromosomes in the GnomAD database, including 538 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 0.078 (538 hom., cov: 30)
• Consequence: CAVIN1 NM_012232.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6	c.471+7895G>C		intron_variant	Intron 1 of 1	ENST00000357037.6	NP_036364.2
CAVIN1	XM_005257242.5	c.472-2482G>C		intron_variant	Intron 1 of 1		XP_005257299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6	c.471+7895G>C		intron_variant	Intron 1 of 1	1	NM_012232.6	ENSP00000349541.4

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11880 AN: 151992 Hom.: 535 Cov.: 30

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0859

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

GnomAD4 genome AF: 0.0782 AC: 11898 AN: 152110 Hom.: 538 Cov.: 30 AF XY: 0.0790 AC XY: 5876 AN XY: 74344

African (AFR) AF: 0.0627 AC: 2600 AN: 41498

American (AMR) AF: 0.0753 AC: 1150 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.242 AC: 1248 AN: 5158

South Asian (SAS) AF: 0.0911 AC: 439 AN: 4818

European-Finnish (FIN) AF: 0.0669 AC: 709 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5157 AN: 67992

Other (OTH) AF: 0.0869 AC: 183 AN: 2106

Alfa AF: 0.0199 Hom.: 12

Bravo AF: 0.0774

Asia WGS AF: 0.161 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		0.23
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: rs2062213; hg19: chr17-40566750;