Genetic Variant CBARP:p.Gly427Val (chr19-1230975-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152769.3(CBARP):c.1280G>T(p.Gly427Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CBARP
NM_152769.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200

Publications

0 publications found

Variant links:

Genes affected

CBARP (HGNC:28617): (CACN subunit beta associated regulatory protein) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in negative regulation of calcium ion-dependent exocytosis and negative regulation of voltage-gated calcium channel activity. Predicted to be located in synaptic vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Predicted to colocalize with growth cone and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

CBARP links:

CBARP-DT (HGNC:55285): (CBARP divergent transcript)

CBARP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060112327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152769.3. 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
	CBARP	NM_001393918.1	MANE Select	c.1154+126G>T		intron	N/A	NP_001380847.1	Q8N350-3
	CBARP	NM_152769.3		c.1280G>T	p.Gly427Val	missense	Exon 9 of 9	NP_689982.3	Q8N350-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CBARP	ENST00000590083.5	TSL:1	c.1280G>T	p.Gly427Val	missense	Exon 9 of 9	ENSP00000465260.1	Q8N350-4
CBARP	ENST00000650044.2	MANE Select	c.1154+126G>T		intron	N/A	ENSP00000497208.1	Q8N350-3
CBARP	ENST00000917007.1		c.1280G>T	p.Gly427Val	missense	Exon 9 of 10	ENSP00000587066.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

200434

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1407328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694526

African (AFR)

AF:

0.00

AC:

AN:

31690

American (AMR)

AF:

0.00

AC:

AN:

37820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23016

East Asian (EAS)

AF:

0.00

AC:

AN:

38948

South Asian (SAS)

AF:

0.00

AC:

AN:

78958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083770

Other (OTH)

AF:

0.00

AC:

AN:

57952

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000827

AC:

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

0.087

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.31

M_CAP

Benign

0.016

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

PhyloP100

-0.020

Sift4G

Benign

0.24

Vest4

0.060

MVP

0.29

MPC

0.12

ClinPred

0.056

GERP RS

-0.27

gMVP

0.11

Mutation Taster

=93/7

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over