Genetic Variant CABP5:p.Arg21Gln (chr19-48043861-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019855.5(CABP5):c.62G>A(p.Arg21Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,500,978 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

CABP5
NM_019855.5 missense, splice_region

Scores

Splicing: ADA: 0.001648

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.423

Publications

3 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01572612).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019855.5. 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
	CABP5	NM_019855.5	MANE Select	c.62G>A	p.Arg21Gln	missense splice_region	Exon 1 of 6	NP_062829.1	Q9NP86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP5	ENST00000293255.3	TSL:1 MANE Select	c.62G>A	p.Arg21Gln	missense splice_region	Exon 1 of 6	ENSP00000293255.1	Q9NP86
	CABP5	ENST00000602032.1	TSL:3	n.21G>A		splice_region non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000978

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000745

AC:

AN:

161080

AF XY:

0.0000560

show subpopulations

Gnomad AFR exome

AF:

0.0000919

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

205

AN:

1348920

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

109

AN XY:

665828

show subpopulations

African (AFR)

AF:

0.000749

AC:

AN:

26696

American (AMR)

AF:

0.00

AC:

AN:

23256

Ashkenazi Jewish (ASJ)

AF:

0.0000454

AC:

AN:

22038

East Asian (EAS)

AF:

0.00248

AC:

AN:

31874

South Asian (SAS)

AF:

0.0000283

AC:

AN:

70550

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52058

Middle Eastern (MID)

AF:

0.00176

AC:

AN:

5108

European-Non Finnish (NFE)

AF:

0.0000687

AC:

AN:

1061976

Other (OTH)

AF:

0.000361

AC:

AN:

55364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000986

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41508

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000981

AC:

AN:

5098

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000100

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.011

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.37

M_CAP

Benign

0.0034

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.14

PhyloP100

0.42

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.13

REVEL

Benign

0.089

Sift

Benign

0.60

Sift4G

Benign

0.62

Polyphen

0.0030

Vest4

0.061

MVP

0.39

MPC

0.29

ClinPred

0.055

GERP RS

4.9

PromoterAI

-0.056

Neutral

(source)

Varity_R

0.11

gMVP

0.41

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over