rs963987

Variant names:

• chr17-42409661-A-G
• rs963987
• NM_012232.6:c.472-4273T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-42409661-A-G
• chr17-42409661-A-T

Variant summary

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

The NM_012232.6(CAVIN1):​c.472-4273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,782 control chromosomes in the GnomAD database, including 26,458 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 0.55 (26458 hom., cov: 29)
• Consequence: CAVIN1 NM_012232.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• 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

ENSG00000289579 (HGNC:58351):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN1	NM_012232.6	c.472-4273T>C		intron_variant	Intron 1 of 1	ENST00000357037.6	NP_036364.2
CAVIN1	XM_005257242.5	c.*2383T>C		downstream_gene_variant			XP_005257299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN1	ENST00000357037.6	c.472-4273T>C		intron_variant	Intron 1 of 1	1	NM_012232.6	ENSP00000349541.4
ENSG00000289579	ENST00000691590.1	n.*231T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83228 AN: 151664 Hom.: 26459 Cov.: 29

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.548 AC: 83221 AN: 151782 Hom.: 26458 Cov.: 29 AF XY: 0.546 AC XY: 40517 AN XY: 74164

African (AFR) AF: 0.206 AC: 8510 AN: 41390

American (AMR) AF: 0.706 AC: 10747 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2695 AN: 3466

East Asian (EAS) AF: 0.590 AC: 3029 AN: 5136

South Asian (SAS) AF: 0.527 AC: 2534 AN: 4808

European-Finnish (FIN) AF: 0.640 AC: 6735 AN: 10520

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46980 AN: 67928

Other (OTH) AF: 0.596 AC: 1257 AN: 2110

Alfa AF: 0.621 Hom.: 6671

Bravo AF: 0.542

Asia WGS AF: 0.471 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.1
DANN	Benign	0.73
PhyloP100		0.33
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: rs963987; hg19: chr17-40561679;