NM_001393918.1:c.218G>A

Variant names:

• chr19-1235806-C-T
• rs752257864
• NM_001393918.1:c.218G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001393918.1(CBARP):​c.218G>A​(p.Cys73Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CBARP NM_001393918.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393918.1. 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.218G>A	p.Cys73Tyr	missense	Exon 3 of 10	NP_001380847.1	Q8N350-3
	CBARP	NM_152769.3		c.218G>A	p.Cys73Tyr	missense	Exon 3 of 9	NP_689982.3	Q8N350-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBARP	ENST00000650044.2	MANE Select	c.218G>A	p.Cys73Tyr	missense	Exon 3 of 10	ENSP00000497208.1	Q8N350-3
	CBARP	ENST00000590083.5	TSL:1	c.218G>A	p.Cys73Tyr	missense	Exon 3 of 9	ENSP00000465260.1	Q8N350-4
	CBARP	ENST00000917007.1		c.218G>A	p.Cys73Tyr	missense	Exon 3 of 10	ENSP00000587066.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246722 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: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456976 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725104

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000315 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.46	T
PhyloP100		4.8
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Vest4		0.95
MVP		0.72
MPC		0.65
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.70
gMVP		0.53
Mutation Taster		=15/85	disease causing

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

Other links and lift over

dbSNP: rs752257864; hg19: chr19-1235805;