rs7210713

Variant names:

• chr17-42402983-G-C
• rs7210713
• NM_012232.6:c.*1704C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-42402983-G-C
• chr17-42402983-G-A
• chr17-42402983-G-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.*1704C>G 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 152,446 control chromosomes in the GnomAD database, including 55,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (55314 hom., cov: 32)
  • Exomes 𝑓: 0.94 (129 hom.)
• Consequence: CAVIN1 NM_012232.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.495
• Publications: 14 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=-0.91).
• BP6: Variant 17-42402983-G-C is Benign according to our data. Variant chr17-42402983-G-C is described in ClinVar as Benign. ClinVar VariationId is 323259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 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.*1704C>G		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.*1704C>G		3_prime_UTR	Exon 2 of 2	ENSP00000349541.4	Q6NZI2-1
	CAVIN1	ENST00000870236.1		c.*1704C>G		3_prime_UTR	Exon 2 of 2	ENSP00000540295.1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128464 AN: 152036 Hom.: 55279 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.938 AC: 274 AN: 292 Hom.: 129 Cov.: 0 AF XY: 0.941 AC XY: 207 AN XY: 220

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.941 AC: 241 AN: 256

Other (OTH) AF: 0.917 AC: 11 AN: 12

GnomAD4 genome AF: 0.845 AC: 128552 AN: 152154 Hom.: 55314 Cov.: 32 AF XY: 0.848 AC XY: 63057 AN XY: 74380

African (AFR) AF: 0.658 AC: 27271 AN: 41454

American (AMR) AF: 0.918 AC: 14045 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3296 AN: 3468

East Asian (EAS) AF: 0.989 AC: 5125 AN: 5182

South Asian (SAS) AF: 0.954 AC: 4594 AN: 4814

European-Finnish (FIN) AF: 0.898 AC: 9513 AN: 10598

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

European-Non Finnish (NFE) AF: 0.908 AC: 61753 AN: 68022

Other (OTH) AF: 0.873 AC: 1847 AN: 2116

Alfa AF: 0.849 Hom.: 2828

Bravo AF: 0.837

Asia WGS AF: 0.957 AC: 3327 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	-0.91
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		-0.49
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: rs7210713; hg19: chr17-40555001;