rs11062040

Positions:

• chr12-1982091-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000280665.11(DCP1B):​c.319+11173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,870 control chromosomes in the GnomAD database, including 22,809 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 0.54 (22809 hom., cov: 32)
• Consequence: DCP1B ENST00000280665.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

DCP1B (HGNC:24451): (decapping mRNA 1B) This gene encodes a member of a family of proteins that function in removing the 5' cap from mRNAs, which is a step in regulated mRNA decay. This protein localizes to cytoplasmic foci which are the site of mRNA breakdown and turnover. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCP1B	NM_152640.5	c.319+11173G>A		intron_variant		ENST00000280665.11	NP_689853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCP1B	ENST00000280665.11	c.319+11173G>A		intron_variant		1	NM_152640.5	ENSP00000280665	P1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82225 AN: 151750 Hom.: 22786 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.542 AC: 82307 AN: 151870 Hom.: 22809 Cov.: 32 AF XY: 0.538 AC XY: 39952 AN XY: 74226

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.556

Alfa AF: 0.504 Hom.: 43347

Bravo AF: 0.551

Asia WGS AF: 0.487 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs11062040; hg19: chr12-2091257;