19-1234248-G-C

Variant names:

• chr19-1234248-G-C
• rs866563653
• NM_001393918.1:c.711C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001393918.1(CBARP):​c.711C>G​(p.Ala237Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CBARP NM_001393918.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.212
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-0.212 with no splicing effect.

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.711C>G	p.Ala237Ala	synonymous	Exon 7 of 10	NP_001380847.1	Q8N350-3
	CBARP	NM_152769.3		c.711C>G	p.Ala237Ala	synonymous	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.711C>G	p.Ala237Ala	synonymous	Exon 7 of 10	ENSP00000497208.1	Q8N350-3
	CBARP	ENST00000590083.5	TSL:1	c.711C>G	p.Ala237Ala	synonymous	Exon 7 of 9	ENSP00000465260.1	Q8N350-4
	CBARP	ENST00000917007.1		c.711C>G	p.Ala237Ala	synonymous	Exon 7 of 10	ENSP00000587066.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331902 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 651080

African (AFR) AF: 0.00 AC: 0 AN: 29338

American (AMR) AF: 0.00 AC: 0 AN: 22912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35614

South Asian (SAS) AF: 0.00 AC: 0 AN: 67072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45984

Middle Eastern (MID) AF: 0.000189 AC: 1 AN: 5288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050646

Other (OTH) AF: 0.00 AC: 0 AN: 54892

GnomAD4 genome Cov.: 34

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.48
PhyloP100		-0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs866563653; hg19: chr19-1234247;