rs7212299

Variant names:

• chr17-42402938-A-G
• rs7212299
• NM_012232.6:c.*1749T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-42402938-A-G
• chr17-42402938-A-C
• chr17-42402938-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012232.6(CAVIN1):​c.*1749T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,140 control chromosomes in the GnomAD database, including 55,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55286 hom., cov: 30)
  • Exomes 𝑓: 0.92 (44 hom.)
• Consequence: CAVIN1 NM_012232.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.538
• Publications: 13 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):

• lipodystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital generalized lipodystrophy type 4

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-42402938-A-G is Benign according to our data. Variant chr17-42402938-A-G is described in ClinVar as Benign. ClinVar VariationId is 323258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012232.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN1	NM_012232.6	MANE Select	c.*1749T>C		3_prime_UTR	Exon 2 of 2	NP_036364.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN1	ENST00000357037.6	TSL:1 MANE Select	c.*1749T>C		3_prime_UTR	Exon 2 of 2	ENSP00000349541.4	Q6NZI2-1
	CAVIN1	ENST00000870236.1		c.*1749T>C		3_prime_UTR	Exon 2 of 2	ENSP00000540295.1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128383 AN: 151918 Hom.: 55251 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.923 AC: 96 AN: 104 Hom.: 44 Cov.: 0 AF XY: 0.938 AC XY: 75 AN XY: 80

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.875 AC: 14 AN: 16

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 8 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.934 AC: 71 AN: 76

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.845 AC: 128471 AN: 152036 Hom.: 55286 Cov.: 30 AF XY: 0.848 AC XY: 63026 AN XY: 74318

African (AFR) AF: 0.658 AC: 27265 AN: 41426

American (AMR) AF: 0.918 AC: 14027 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3294 AN: 3466

East Asian (EAS) AF: 0.989 AC: 5114 AN: 5170

South Asian (SAS) AF: 0.953 AC: 4587 AN: 4812

European-Finnish (FIN) AF: 0.898 AC: 9514 AN: 10590

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61721 AN: 67986

Other (OTH) AF: 0.873 AC: 1842 AN: 2110

Alfa AF: 0.871 Hom.: 10307

Bravo AF: 0.837

Asia WGS AF: 0.956 AC: 3325 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital generalized lipodystrophy type 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.25
PhyloP100		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs7212299; hg19: chr17-40554956;