rs12423058

chr12-1955500-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152640.5(DCP1B):c.583A>G(p.Asn195Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,832 control chromosomes in the GnomAD database, including 1,112 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.026 (77 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1035 hom.)
• Consequence: DCP1B NM_152640.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007843405).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0261 (3972/152296) while in subpopulation NFE AF= 0.0392 (2666/68028). AF 95% confidence interval is 0.0379. There are 77 homozygotes in gnomad4. There are 1945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 77 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCP1B	NM_152640.5	c.583A>G	p.Asn195Asp	missense_variant	6/9	ENST00000280665.11
DCP1B	NR_135060.2	n.735A>G		non_coding_transcript_exon_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCP1B	ENST00000280665.11	c.583A>G	p.Asn195Asp	missense_variant	6/9	1	NM_152640.5	P1

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3974 AN: 152178 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0256 AC: 6442 AN: 251388 Hom.: 122 AF XY: 0.0255 AC XY: 3469 AN XY: 135864

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.0134

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00732

Gnomad FIN exome AF: 0.0512

Gnomad NFE exome AF: 0.0378

Gnomad OTH exome AF: 0.0251

GnomAD4 exome AF: 0.0348 AC: 50789 AN: 1461536 Hom.: 1035 Cov.: 31 AF XY: 0.0342 AC XY: 24893 AN XY: 727080

Gnomad4 AFR exome AF: 0.00427

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00812

Gnomad4 FIN exome AF: 0.0506

Gnomad4 NFE exome AF: 0.0399

Gnomad4 OTH exome AF: 0.0310

GnomAD4 genome AF: 0.0261 AC: 3972 AN: 152296 Hom.: 77 Cov.: 32 AF XY: 0.0261 AC XY: 1945 AN XY: 74466

Gnomad4 AFR AF: 0.00611

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0327 Hom.: 47

Bravo AF: 0.0232

TwinsUK AF: 0.0383 AC: 142

ALSPAC AF: 0.0363 AC: 140

ESP6500AA AF: 0.00862 AC: 38

ESP6500EA AF: 0.0362 AC: 311

ExAC AF: 0.0255 AC: 3098

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0352

EpiControl AF: 0.0363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.090	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0078	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	0.89	D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.083
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.99	D;.
Vest4		0.42
MPC		0.34
ClinPred		0.020	T
GERP RS		5.7
Varity_R		0.43
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12423058; hg19: chr12-2064666; COSMIC: COSV54973265;