Genetic Variant CAVIN3:p.Ala218Ala (chr11-6319295-A-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_145040.3(CAVIN3):c.654T>A(p.Ala218Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,608,630 control chromosomes in the GnomAD database, including 375,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 33020 hom., cov: 34)

Exomes 𝑓: 0.68 ( 342713 hom. )

Consequence

CAVIN3
NM_145040.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.254

Publications

18 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-0.254 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN3	NM_145040.3 link	c.654T>A	p.Ala218Ala	synonymous_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.654T>A	p.Ala218Ala	synonymous_variant	Exon 2 of 2	1	NM_145040.3	ENSP00000307292.3		Q969G5

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99526

AN:

151998

Hom.:

33010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.827

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.708

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.650

GnomAD2 exomes

AF:

0.682

AC:

165955

AN:

243258

AF XY:

0.690

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.713

Gnomad EAS exome

AF:

0.764

Gnomad FIN exome

AF:

0.753

Gnomad NFE exome

AF:

0.699

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.685

AC:

997331

AN:

1456514

Hom.:

342713

Cov.:

AF XY:

0.687

AC XY:

497241

AN XY:

724268

show subpopulations

African (AFR)

AF:

0.547

AC:

18175

AN:

33216

American (AMR)

AF:

0.572

AC:

25042

AN:

43782

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

18464

AN:

25816

East Asian (EAS)

AF:

0.718

AC:

28437

AN:

39632

South Asian (SAS)

AF:

0.714

AC:

61131

AN:

85564

European-Finnish (FIN)

AF:

0.751

AC:

39943

AN:

53182

Middle Eastern (MID)

AF:

0.670

AC:

3813

AN:

5688

European-Non Finnish (NFE)

AF:

0.686

AC:

761574

AN:

1109562

Other (OTH)

AF:

0.678

AC:

40752

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

19205

38411

57616

76822

96027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19468

38936

58404

77872

97340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.655

AC:

99575

AN:

152116

Hom.:

33020

Cov.:

AF XY:

0.657

AC XY:

48877

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.553

AC:

22919

AN:

41482

American (AMR)

AF:

0.623

AC:

9534

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2452

AN:

3470

East Asian (EAS)

AF:

0.745

AC:

3846

AN:

5164

South Asian (SAS)

AF:

0.710

AC:

3429

AN:

4832

European-Finnish (FIN)

AF:

0.747

AC:

7901

AN:

10574

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.694

AC:

47156

AN:

67982

Other (OTH)

AF:

0.647

AC:

1365

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1794

3588

5382

7176

8970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.673

Hom.:

8440

Bravo

AF:

0.638

Asia WGS

AF:

0.688

AC:

2396

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.9

(source)

DANN

Benign

0.84

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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