dbSNP rs1051992: CAVIN3:p.Leu158Pro (chr11-6319476-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20612 hom., cov: 34)

Exomes 𝑓: 0.55 ( 219133 hom. )

Consequence

CAVIN3
NM_145040.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

45 publications found

Variant links:

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 links:

ENSG00000282556 (HGNC:):

ENSG00000282556 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CAVIN3	NM_145040.3 link	c.473T>C	p.Leu158Pro	missense_variant	Exon 2 of 2	ENST00000303927.4	NP_659477.2	Q969G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4 link	c.473T>C	p.Leu158Pro	missense_variant	Exon 2 of 2	1	NM_145040.3	ENSP00000307292.3		Q969G5

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78272

AN:

152032

Hom.:

20604

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.550

AC:

130009

AN:

236392

AF XY:

0.559

show subpopulations

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 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.:

AF XY:

0.550

AC XY:

397635

AN XY:

723450

show subpopulations

African (AFR)

AF:

0.388

AC:

12948

AN:

33366

American (AMR)

AF:

0.463

AC:

20453

AN:

44156

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

13834

AN:

25872

East Asian (EAS)

AF:

0.612

AC:

24302

AN:

39678

South Asian (SAS)

AF:

0.612

AC:

52406

AN:

85672

European-Finnish (FIN)

AF:

0.640

AC:

31338

AN:

48960

Middle Eastern (MID)

AF:

0.496

AC:

2851

AN:

5752

European-Non Finnish (NFE)

AF:

0.545

AC:

604728

AN:

1110446

Other (OTH)

AF:

0.537

AC:

32265

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

21783

43565

65348

87130

108913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.515

AC:

78313

AN:

152152

Hom.:

20612

Cov.:

AF XY:

0.520

AC XY:

38703

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.395

AC:

16411

AN:

41520

American (AMR)

AF:

0.507

AC:

7749

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

1880

AN:

3466

East Asian (EAS)

AF:

0.633

AC:

3274

AN:

5174

South Asian (SAS)

AF:

0.602

AC:

2906

AN:

4828

European-Finnish (FIN)

AF:

0.644

AC:

6818

AN:

10582

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37444

AN:

67976

Other (OTH)

AF:

0.495

AC:

1047

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2004

4008

6013

8017

10021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.542

Hom.:

69871

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.6

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0000033

T;T

MetaSVM

Benign

-0.93

PhyloP100

-1.7

PrimateAI

Benign

0.38

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

GERP RS

-3.6

Varity_R

0.10

gMVP

0.039

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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rs1051992

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over