NM_172364.5:c.*1690C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_172364.5(CACNA2D4):​c.*1690C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA2D4
NM_172364.5 splice_region

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.893
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA2D4NM_172364.5 linkc.*1690C>T splice_region_variant Exon 38 of 38 ENST00000382722.10 NP_758952.4 Q7Z3S7-1
CACNA2D4NM_172364.5 linkc.*1690C>T 3_prime_UTR_variant Exon 38 of 38 ENST00000382722.10 NP_758952.4 Q7Z3S7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA2D4ENST00000382722.10 linkc.*1690C>T splice_region_variant Exon 38 of 38 1 NM_172364.5 ENSP00000372169.4 Q7Z3S7-1
CACNA2D4ENST00000382722 linkc.*1690C>T 3_prime_UTR_variant Exon 38 of 38 1 NM_172364.5 ENSP00000372169.4 Q7Z3S7-1
CACNA2D4ENST00000537784.5 linkn.*2297C>T splice_region_variant, non_coding_transcript_exon_variant Exon 15 of 15 1 ENSP00000440231.2 X6RLU5
CACNA2D4ENST00000537784.5 linkn.*2297C>T 3_prime_UTR_variant Exon 15 of 15 1 ENSP00000440231.2 X6RLU5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
33
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
6
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
4
Gnomad4 FIN exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
4.0
DANN
Benign
0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs533040733; hg19: chr12-1901131; API