NM_014329.5:c.747T>C

Variant names:

• chr16-67877614-T-C
• rs8060686
• NM_014329.5:c.747T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014329.5(EDC4):​c.747T>C​(p.Cys249Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,613,906 control chromosomes in the GnomAD database, including 42,035 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 (10628 hom., cov: 32)
  • Exomes 𝑓: 0.19 (31407 hom.)
• Consequence: EDC4 NM_014329.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 67 publications found

Genes affected

EDC4 (HGNC:17157): (enhancer of mRNA decapping 4) Predicted to be involved in deadenylation-independent decapping of nuclear-transcribed mRNA. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014329.5. 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
	EDC4	NM_014329.5	MANE Select	c.747T>C	p.Cys249Cys	synonymous	Exon 6 of 29	NP_055144.3
	EDC4	NM_001427345.1		c.747T>C	p.Cys249Cys	synonymous	Exon 6 of 28	NP_001414274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDC4	ENST00000358933.10	TSL:1 MANE Select	c.747T>C	p.Cys249Cys	synonymous	Exon 6 of 29	ENSP00000351811.5
	EDC4	ENST00000573992.5	TSL:1	n.126T>C		non_coding_transcript_exon	Exon 1 of 24
	EDC4	ENST00000851723.1		c.747T>C	p.Cys249Cys	synonymous	Exon 6 of 29	ENSP00000521782.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47333 AN: 151928 Hom.: 10594 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.283

GnomAD2 exomes AF: 0.230 AC: 57725 AN: 251382 AF XY: 0.219

Gnomad AFR exome AF: 0.648

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.0658

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.189 AC: 276482 AN: 1461862 Hom.: 31407 Cov.: 34 AF XY: 0.189 AC XY: 137741 AN XY: 727236

African (AFR) AF: 0.656 AC: 21971 AN: 33480

American (AMR) AF: 0.297 AC: 13284 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5118 AN: 26136

East Asian (EAS) AF: 0.0731 AC: 2901 AN: 39700

South Asian (SAS) AF: 0.248 AC: 21406 AN: 86258

European-Finnish (FIN) AF: 0.190 AC: 10161 AN: 53394

Middle Eastern (MID) AF: 0.256 AC: 1477 AN: 5768

European-Non Finnish (NFE) AF: 0.169 AC: 187555 AN: 1112010

Other (OTH) AF: 0.209 AC: 12609 AN: 60396

GnomAD4 genome AF: 0.312 AC: 47418 AN: 152044 Hom.: 10628 Cov.: 32 AF XY: 0.309 AC XY: 22989 AN XY: 74356

African (AFR) AF: 0.637 AC: 26410 AN: 41436

American (AMR) AF: 0.271 AC: 4141 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3470

East Asian (EAS) AF: 0.0715 AC: 369 AN: 5162

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10588

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11789 AN: 67954

Other (OTH) AF: 0.284 AC: 600 AN: 2112

Alfa AF: 0.210 Hom.: 21443

Bravo AF: 0.330

Asia WGS AF: 0.229 AC: 799 AN: 3478

EpiCase AF: 0.173

EpiControl AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.4
DANN	Benign	0.45
PhyloP100		0.38
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8060686; hg19: chr16-67911517; COSMIC: COSV62765921; COSMIC: COSV62765921;