rs11062040

Variant names:

• chr12-1982091-C-T
• rs11062040
• NM_152640.5:c.319+11173G>A

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+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 NM_152640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 17 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: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• 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: Orphanet, ClinGen
• 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: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1B	NM_152640.5	MANE Select	c.319+11173G>A		intron	N/A	NP_689853.3
	DCP1B	NR_135060.2		n.471+9030G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1B	ENST00000280665.11	TSL:1 MANE Select	c.319+11173G>A		intron	N/A	ENSP00000280665.6
	CACNA1C	ENST00000682544.1		c.139+10890C>T		intron	N/A	ENSP00000507184.1
	CACNA1C	ENST00000683824.1		c.139+10890C>T		intron	N/A	ENSP00000507867.1

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

African (AFR) AF: 0.661 AC: 27401 AN: 41440

American (AMR) AF: 0.516 AC: 7879 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1678 AN: 3460

East Asian (EAS) AF: 0.527 AC: 2721 AN: 5162

South Asian (SAS) AF: 0.426 AC: 2054 AN: 4816

European-Finnish (FIN) AF: 0.467 AC: 4914 AN: 10524

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.500 AC: 33964 AN: 67890

Other (OTH) AF: 0.556 AC: 1173 AN: 2110

Alfa AF: 0.512 Hom.: 92027

Bravo AF: 0.551

Asia WGS AF: 0.487 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.044
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: rs11062040; hg19: chr12-2091257;