Variant 12-1793739-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_172364.5(CACNA2D4):c.3330C>G(p.Gly1110Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CACNA2D4
NM_172364.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.38

Variant links:

Genes affected

CACNA2D4 (HGNC:20202): (calcium voltage-gated channel auxiliary subunit alpha2delta 4) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CACNA2D4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-5.38 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D4	NM_172364.5 link	c.3330C>G	p.Gly1110Gly	synonymous_variant	38/38	ENST00000382722.10	NP_758952.4	Q7Z3S7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNA2D4	ENST00000382722.10 link	c.3330C>G	p.Gly1110Gly	synonymous_variant	38/38	1	NM_172364.5	ENSP00000372169.4	Q7Z3S7-1
CACNA2D4	ENST00000587995.5 link	c.3255C>G	p.Gly1085Gly	synonymous_variant	37/37	5		ENSP00000465372.1	K7EJY1
CACNA2D4	ENST00000588077.5 link	c.3138C>G	p.Gly1046Gly	synonymous_variant	38/38	5		ENSP00000468530.1	Q7Z3S7-4
CACNA2D4	ENST00000536846.6 link	c.768C>G	p.Gly256Gly	synonymous_variant	12/12	5		ENSP00000468167.1	K7ER98
CACNA2D4	ENST00000538027.6 link	c.765C>G	p.Gly255Gly	synonymous_variant	12/12	5		ENSP00000443038.2	X6RLY7
CACNA2D4	ENST00000538450.5 link	c.720C>G	p.Gly240Gly	synonymous_variant	11/11	2		ENSP00000446341.1	B4DVU4
CACNA2D4	ENST00000444595.6 link	n.*1514C>G		non_coding_transcript_exon_variant	37/37	1		ENSP00000403371.2	E7EUE0
CACNA2D4	ENST00000537784.5 link	n.*523C>G		non_coding_transcript_exon_variant	15/15	1		ENSP00000440231.2	X6RLU5
CACNA2D4	ENST00000545595.6 link	n.*523C>G		non_coding_transcript_exon_variant	10/10	1		ENSP00000442329.2	Q7Z3S7-7
CACNA2D4	ENST00000585385.5 link	n.*523C>G		non_coding_transcript_exon_variant	11/11	5		ENSP00000467333.1	K7EIY9
CACNA2D4	ENST00000444595.6 link	n.*1514C>G		3_prime_UTR_variant	37/37	1		ENSP00000403371.2	E7EUE0
CACNA2D4	ENST00000537784.5 link	n.*523C>G		3_prime_UTR_variant	15/15	1		ENSP00000440231.2	X6RLU5
CACNA2D4	ENST00000545595.6 link	n.*523C>G		3_prime_UTR_variant	10/10	1		ENSP00000442329.2	Q7Z3S7-7
CACNA2D4	ENST00000585385.5 link	n.*523C>G		3_prime_UTR_variant	11/11	5		ENSP00000467333.1	K7EIY9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245934

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0060

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over