rs12423058

Variant names:

• chr12-1955500-T-C
• rs12423058
• NM_152640.5:c.583A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting 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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -9 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 77 AR gene

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.583A>G	p.Asn195Asp	missense	Exon 6 of 9	NP_689853.3
	DCP1B	NR_135060.2		n.735A>G		non_coding_transcript_exon	Exon 7 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1B	ENST00000280665.11	TSL:1 MANE Select	c.583A>G	p.Asn195Asp	missense	Exon 6 of 9	ENSP00000280665.6	Q8IZD4-1
	DCP1B	ENST00000971563.1		c.583A>G	p.Asn195Asp	missense	Exon 6 of 10	ENSP00000641622.1
	DCP1B	ENST00000883051.1		c.664A>G	p.Asn222Asp	missense	Exon 6 of 9	ENSP00000553110.1

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

GnomAD2 exomes AF: 0.0256 AC: 6442 AN: 251388 AF XY: 0.0255

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 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

African (AFR) AF: 0.00427 AC: 143 AN: 33474

American (AMR) AF: 0.0145 AC: 647 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 290 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00812 AC: 700 AN: 86238

European-Finnish (FIN) AF: 0.0506 AC: 2704 AN: 53392

Middle Eastern (MID) AF: 0.0147 AC: 85 AN: 5766

European-Non Finnish (NFE) AF: 0.0399 AC: 44347 AN: 1111758

Other (OTH) AF: 0.0310 AC: 1873 AN: 60388

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

African (AFR) AF: 0.00611 AC: 254 AN: 41570

American (AMR) AF: 0.0190 AC: 290 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4826

European-Finnish (FIN) AF: 0.0550 AC: 583 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0392 AC: 2666 AN: 68028

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0338 Hom.: 184

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 v4.9

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
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.0
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.083
Sift	Uncertain	0.017	D
Sift4G	Benign	0.12	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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12423058; hg19: chr12-2064666; COSMIC: COSV54973265;