12-1988550-T-C

Variant names:

• chr12-1988550-T-C
• rs4141130
• NM_152640.5:c.319+4714A>G

Variant summary

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

The NM_152640.5(DCP1B):​c.319+4714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,100 control chromosomes in the GnomAD database, including 7,554 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 0.31 (7554 hom., cov: 32)
• Consequence: DCP1B NM_152640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 5 publications found

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]

CACNA1C Gene-Disease associations (from GenCC):

• Timothy syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• long QT syndrome 8

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• Brugada syndrome

  Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
• Brugada syndrome 3

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• short QT syndrome

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

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 (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1B	NM_152640.5	MANE Select	c.319+4714A>G		intron	N/A	NP_689853.3
	DCP1B	NR_135060.2		n.471+2571A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1B	ENST00000280665.11	TSL:1 MANE Select	c.319+4714A>G		intron	N/A	ENSP00000280665.6	Q8IZD4-1
	CACNA1C	ENST00000682544.1		c.139+17349T>C		intron	N/A	ENSP00000507184.1	A0A804HIR0
	CACNA1C	ENST00000683824.1		c.139+17349T>C		intron	N/A	ENSP00000507867.1	A0A804HKC4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47150 AN: 151982 Hom.: 7549 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.310 AC: 47172 AN: 152100 Hom.: 7554 Cov.: 32 AF XY: 0.308 AC XY: 22883 AN XY: 74368

African (AFR) AF: 0.304 AC: 12613 AN: 41466

American (AMR) AF: 0.275 AC: 4204 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2768 AN: 5164

South Asian (SAS) AF: 0.230 AC: 1111 AN: 4824

European-Finnish (FIN) AF: 0.279 AC: 2952 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21463 AN: 67988

Other (OTH) AF: 0.319 AC: 673 AN: 2112

Alfa AF: 0.314 Hom.: 32605

Bravo AF: 0.309

Asia WGS AF: 0.385 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.45
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs4141130; hg19: chr12-2097716;