3-53344218-C-T

Variant names:

• chr3-53344218-C-T
• rs2029213
• NM_018403.7:c.176+684G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018403.7(DCP1A):​c.176+684G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,826 control chromosomes in the GnomAD database, including 7,403 homozygotes. 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: 𝑓 0.29 (7403 hom., cov: 32)
• Consequence: DCP1A NM_018403.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 7 publications found

Genes affected

DCP1A (HGNC:18714): (decapping mRNA 1A) Decapping is a key step in general and regulated mRNA decay. The protein encoded by this gene is a decapping enzyme. This protein and another decapping enzyme form a decapping complex, which interacts with the nonsense-mediated decay factor hUpf1 and may be recruited to mRNAs containing premature termination codons. This protein also participates in the TGF-beta signaling pathway. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CACNA1D Gene-Disease associations (from GenCC):

• aldosterone-producing adenoma with seizures and neurological abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• sinoatrial node dysfunction and deafness

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCP1A	NM_018403.7	c.176+684G>A		intron_variant	Intron 2 of 9	ENST00000610213.6	NP_060873.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCP1A	ENST00000610213.6	c.176+684G>A		intron_variant	Intron 2 of 9	1	NM_018403.7	ENSP00000476386.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43442 AN: 151714 Hom.: 7396 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43452 AN: 151826 Hom.: 7403 Cov.: 32 AF XY: 0.286 AC XY: 21246 AN XY: 74176

African (AFR) AF: 0.109 AC: 4532 AN: 41458

American (AMR) AF: 0.388 AC: 5922 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1609 AN: 5146

South Asian (SAS) AF: 0.185 AC: 893 AN: 4822

European-Finnish (FIN) AF: 0.361 AC: 3774 AN: 10464

Middle Eastern (MID) AF: 0.330 AC: 95 AN: 288

European-Non Finnish (NFE) AF: 0.359 AC: 24361 AN: 67898

Other (OTH) AF: 0.288 AC: 608 AN: 2112

Alfa AF: 0.300 Hom.: 5999

Bravo AF: 0.285

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.45
PhyloP100		-1.3

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

Other links and lift over

dbSNP: rs2029213; hg19: chr3-53378245;