chr12-1993289-A-C

Position:

• chr12-1993289-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152640.5(DCP1B):​c.294T>G​(p.Pro98Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,154 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: DCP1B NM_152640.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.105

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]

DCP1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-1993289-A-C is Benign according to our data. Variant chr12-1993289-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2570815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.105 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCP1B	NM_152640.5	c.294T>G	p.Pro98Pro	synonymous_variant	3/9	ENST00000280665.11	NP_689853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCP1B	ENST00000280665.11	c.294T>G	p.Pro98Pro	synonymous_variant	3/9	1	NM_152640.5	ENSP00000280665.6
CACNA1C	ENST00000682544.1	c.139+22088A>C		intron_variant				ENSP00000507184.1
CACNA1C	ENST00000683824.1	c.139+22088A>C		intron_variant				ENSP00000507867.1
CACNA1C	ENST00000682462.1	c.139+22088A>C		intron_variant				ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.139+22088A>C		intron_variant				ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.139+22088A>C		intron_variant				ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.139+22088A>C		intron_variant				ENSP00000506882.1

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152220 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00137 AC: 344 AN: 251420 Hom.: 2 AF XY: 0.00141 AC XY: 192 AN XY: 135880

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00180

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00119 AC: 1741 AN: 1461816 Hom.: 4 Cov.: 31 AF XY: 0.00130 AC XY: 943 AN XY: 727220

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000537

Gnomad4 ASJ exome AF: 0.00188

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00187

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00124 AC: 189 AN: 152338 Hom.: 3 Cov.: 33 AF XY: 0.00119 AC XY: 89 AN XY: 74494

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00219

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.00104

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

DCP1B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Benign	0.81

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: rs150415068; hg19: chr12-2102455; COSMIC: COSV54972783;