rs1051992

Positions:

• chr11-6319476-A-G
• chr11-6319476-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145040.3(CAVIN3):​c.473T>C​(p.Leu158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,606,178 control chromosomes in the GnomAD database, including 239,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (20612 hom., cov: 34)
  • Exomes 𝑓: 0.55 (219133 hom.)
• Consequence: CAVIN3 NM_145040.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

CAVIN3 (HGNC:9400): (caveolae associated protein 3) The protein encoded by this gene was identified as a binding protein of the protein kinase C, delta (PRKCD). The expression of this gene in cultured cell lines is strongly induced by serum starvation. The expression of this protein was found to be down-regulated in various cancer cell lines, suggesting the possible tumor suppressor function of this protein. [provided by RefSeq, Jul 2008]

CAVIN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.296233E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAVIN3	NM_145040.3	c.473T>C	p.Leu158Pro	missense_variant	2/2	ENST00000303927.4	NP_659477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4	c.473T>C	p.Leu158Pro	missense_variant	2/2	1	NM_145040.3	ENSP00000307292.3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78272 AN: 152032 Hom.: 20604 Cov.: 34

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.498

GnomAD3 exomes AF: 0.550 AC: 130009 AN: 236392 Hom.: 36196 AF XY: 0.559 AC XY: 72538 AN XY: 129648

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.614

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.547 AC: 795125 AN: 1454026 Hom.: 219133 Cov.: 62 AF XY: 0.550 AC XY: 397635 AN XY: 723450

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.612

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.537

GnomAD4 genome AF: 0.515 AC: 78313 AN: 152152 Hom.: 20612 Cov.: 34 AF XY: 0.520 AC XY: 38703 AN XY: 74394

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.495

Alfa AF: 0.547 Hom.: 50015

Bravo AF: 0.494

TwinsUK AF: 0.536 AC: 1988

ALSPAC AF: 0.545 AC: 2101

ESP6500AA AF: 0.396 AC: 1736

ESP6500EA AF: 0.540 AC: 4636

ExAC AF: 0.549 AC: 66493

Asia WGS AF: 0.579 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.62
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0000033	T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.19	N;N
REVEL	Benign	0.023
Sift	Benign	0.26	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0	B;.
Vest4		0.093
MPC		0.57
ClinPred		0.0056	T
GERP RS		-3.6
Varity_R		0.10
gMVP		0.039

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051992; hg19: chr11-6340706; COSMIC: COSV58268956; COSMIC: COSV58268956;