Genetic Variant CABP5:p.Val128Ala (chr19-48034328-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_019855.5(CABP5):c.383T>C(p.Val128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,597,842 control chromosomes in the GnomAD database, including 108,724 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.30 ( 7860 hom., cov: 30)

Exomes 𝑓: 0.37 ( 100864 hom. )

Consequence

CABP5
NM_019855.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.82

Publications

21 publications found

Variant links:

Genes affected

CABP5 (HGNC:13714): (calcium binding protein 5) The product of this gene belongs to a subfamily of calcium binding proteins, which share similarity to calmodulin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Expression of this gene is retina-specific. The mouse homolog of this protein has been shown to express in the inner nuclear layer of the retina, suggested its role in neuronal functioning. The specific function of this gene is unknown. [provided by RefSeq, Oct 2009]

CABP5 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=0.010474622).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP5	NM_019855.5 link	c.383T>C	p.Val128Ala	missense_variant	Exon 5 of 6	ENST00000293255.3	NP_062829.1	Q9NP86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP5	ENST00000293255.3 link	c.383T>C	p.Val128Ala	missense_variant	Exon 5 of 6	1	NM_019855.5	ENSP00000293255.1		Q9NP86

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45914

AN:

151806

Hom.:

7863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.0811

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.327

GnomAD2 exomes

AF:

0.325

AC:

77428

AN:

238008

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.0710

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.367

AC:

530527

AN:

1445918

Hom.:

100864

Cov.:

AF XY:

0.368

AC XY:

264467

AN XY:

719042

show subpopulations

African (AFR)

AF:

0.158

AC:

5146

AN:

32654

American (AMR)

AF:

0.244

AC:

10141

AN:

41618

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

11049

AN:

25598

East Asian (EAS)

AF:

0.115

AC:

4468

AN:

38764

South Asian (SAS)

AF:

0.352

AC:

29591

AN:

84088

European-Finnish (FIN)

AF:

0.334

AC:

17733

AN:

53166

Middle Eastern (MID)

AF:

0.434

AC:

2478

AN:

5716

European-Non Finnish (NFE)

AF:

0.388

AC:

428686

AN:

1104722

Other (OTH)

AF:

0.356

AC:

21235

AN:

59592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15591

31182

46773

62364

77955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13098

26196

39294

52392

65490

<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:

0.302

AC:

45914

AN:

151924

Hom.:

7860

Cov.:

AF XY:

0.301

AC XY:

22350

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.165

AC:

6829

AN:

41458

American (AMR)

AF:

0.310

AC:

4726

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1527

AN:

3468

East Asian (EAS)

AF:

0.0809

AC:

417

AN:

5156

South Asian (SAS)

AF:

0.335

AC:

1613

AN:

4808

European-Finnish (FIN)

AF:

0.334

AC:

3525

AN:

10548

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.385

AC:

26157

AN:

67928

Other (OTH)

AF:

0.325

AC:

684

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1522

3043

4565

6086

7608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.364

Hom.:

48920

Bravo

AF:

0.290

TwinsUK

AF:

0.379

AC:

1406

ALSPAC

AF:

0.390

AC:

1502

ESP6500AA

AF:

0.172

AC:

756

ESP6500EA

AF:

0.388

AC:

3333

ExAC

AF:

0.325

AC:

39458

Asia WGS

AF:

0.201

AC:

701

AN:

3478

EpiCase

AF:

0.399

EpiControl

AF:

0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.10

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.021

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.15

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

-3.8

PrimateAI

Benign

0.29

PROVEAN

Benign

2.1

REVEL

Benign

0.075

Sift

Benign

1.0

Sift4G

Benign

0.98

Polyphen

0.0

Vest4

0.017

MPC

0.30

ClinPred

0.0012

GERP RS

-5.2

Varity_R

0.023

gMVP

0.21

Mutation Taster

=100/0

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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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