chr17-42403781-C-T

Variant names:

• chr17-42403781-C-T
• rs1129422
• NM_012232.6:c.*906G>A

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.*906G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,372 control chromosomes in the GnomAD database, including 1,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1838 hom., cov: 31)
  • Exomes 𝑓: 0.12 (4 hom.)
• Consequence: CAVIN1 NM_012232.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.104
• 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):

• 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 17-42403781-C-T is Benign according to our data. Variant chr17-42403781-C-T is described in ClinVar as Benign. ClinVar VariationId is 323266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 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.*906G>A		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.*906G>A		3_prime_UTR	Exon 2 of 2	ENSP00000349541.4	Q6NZI2-1
	CAVIN1	ENST00000944722.1		c.*906G>A		3_prime_UTR	Exon 2 of 2	ENSP00000614781.1
	CAVIN1	ENST00000870236.1		c.*906G>A		3_prime_UTR	Exon 2 of 2	ENSP00000540295.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21788 AN: 151960 Hom.: 1834 Cov.: 31

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.122 AC: 36 AN: 294 Hom.: 4 Cov.: 0 AF XY: 0.105 AC XY: 22 AN XY: 210

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.375 AC: 3 AN: 8

South Asian (SAS) AF: 0.111 AC: 2 AN: 18

European-Finnish (FIN) AF: 0.0938 AC: 9 AN: 96

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.113 AC: 17 AN: 150

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.143 AC: 21801 AN: 152078 Hom.: 1838 Cov.: 31 AF XY: 0.147 AC XY: 10945 AN XY: 74330

African (AFR) AF: 0.0957 AC: 3973 AN: 41514

American (AMR) AF: 0.127 AC: 1931 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3468

East Asian (EAS) AF: 0.370 AC: 1912 AN: 5164

South Asian (SAS) AF: 0.264 AC: 1267 AN: 4808

European-Finnish (FIN) AF: 0.138 AC: 1459 AN: 10574

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

European-Non Finnish (NFE) AF: 0.150 AC: 10182 AN: 67970

Other (OTH) AF: 0.154 AC: 325 AN: 2110

Alfa AF: 0.137 Hom.: 195

Bravo AF: 0.139

Asia WGS AF: 0.317 AC: 1100 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	3.6
DANN	Benign	0.34
PhyloP100		0.10
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: rs1129422; hg19: chr17-40555799;