Variant 19-48043861-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 16/23 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

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:

CABP5 (HGNC:):

CABP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABP5	NM_019855.5 linkuse as main transcript	c.62G>A	p.Arg21Gln	missense_variant, splice_region_variant	1/6	ENST00000293255.3	NP_062829.1	Q9NP86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABP5	ENST00000293255.3 linkuse as main transcript	c.62G>A	p.Arg21Gln	missense_variant, splice_region_variant	1/6	1	NM_019855.5	ENSP00000293255.1		Q9NP86
CABP5	ENST00000602032.1 linkuse as main transcript	n.21G>A		splice_region_variant, non_coding_transcript_exon_variant	1/2	3

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

GnomAD3 exomes

AF:

0.0000745

AC:

AN:

161080

Hom.:

AF XY:

0.0000560

AC XY:

AN XY:

89208

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 SAS exome

AF:

0.00

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

Gnomad4 AFR exome

AF:

0.000749

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000454

Gnomad4 EAS exome

AF:

0.00248

Gnomad4 SAS exome

AF:

0.0000283

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.0000687

Gnomad4 OTH exome

AF:

0.000361

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000981

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000976

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.62G>A (p.R21Q) alteration is located in exon 1 (coding exon 1) of the CABP5 gene. This alteration results from a G to A substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.71

CADD

Benign

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

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

Varity_R

0.11

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over