chr19-1234290-G-T

Variant names:

• chr19-1234290-G-T
• NM_001393918.1:c.669C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001393918.1(CBARP):​c.669C>A​(p.Ser223Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CBARP NM_001393918.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.669C>A	p.Ser223Arg	missense	Exon 7 of 10	NP_001380847.1	Q8N350-3
	CBARP	NM_152769.3		c.669C>A	p.Ser223Arg	missense	Exon 7 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.669C>A	p.Ser223Arg	missense	Exon 7 of 10	ENSP00000497208.1	Q8N350-3
	CBARP	ENST00000590083.5	TSL:1	c.669C>A	p.Ser223Arg	missense	Exon 7 of 9	ENSP00000465260.1	Q8N350-4
	CBARP	ENST00000917007.1		c.669C>A	p.Ser223Arg	missense	Exon 7 of 10	ENSP00000587066.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1299034 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 629736

African (AFR) AF: 0.00 AC: 0 AN: 28364

American (AMR) AF: 0.00 AC: 0 AN: 19876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18890

East Asian (EAS) AF: 0.00 AC: 0 AN: 34568

South Asian (SAS) AF: 0.00 AC: 0 AN: 63162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4960

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1031376

Other (OTH) AF: 0.00 AC: 0 AN: 53558

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.43	T
PhyloP100		4.1
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Vest4		0.68
MVP		0.73
MPC		0.49
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.25
gMVP		0.44
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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

hg19: chr19-1234289;