12-1792226-T-TCTC

Position:

• chr12-1792226-T-TCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_172364.5(CACNA2D4):​c.*1428_*1429insGAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (16508 hom., cov: 0)
  • Exomes 𝑓: 0.46 (2 hom.)
• Consequence: CACNA2D4 NM_172364.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.648

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-1792226-T-TCTC is Benign according to our data. Variant chr12-1792226-T-TCTC is described in ClinVar as [Benign]. Clinvar id is 307801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA2D4	NM_172364.5	c.*1428_*1429insGAG		3_prime_UTR_variant	38/38	ENST00000382722.10	NP_758952.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA2D4	ENST00000382722	c.*1428_*1429insGAG		3_prime_UTR_variant	38/38	1	NM_172364.5	ENSP00000372169.4
CACNA2D4	ENST00000537784.5	n.*2035_*2036insGAG		non_coding_transcript_exon_variant	15/15	1		ENSP00000440231.2
CACNA2D4	ENST00000537784.5	n.*2035_*2036insGAG		3_prime_UTR_variant	15/15	1		ENSP00000440231.2
CACNA2D4	ENST00000280663.12	n.5672_5673insGAG		non_coding_transcript_exon_variant	36/36	2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66202 AN: 151852 Hom.: 16506 Cov.: 0

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.464 AC: 13 AN: 28 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 9 AN XY: 18

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.436 AC: 66208 AN: 151970 Hom.: 16508 Cov.: 0 AF XY: 0.435 AC XY: 32334 AN XY: 74266

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.424

Alfa AF: 0.239 Hom.: 686

Bravo AF: 0.412

Asia WGS AF: 0.424 AC: 1478 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone dystrophy 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77487055; hg19: chr12-1901392;