rs8060686

chr16-67877614-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014329.5(EDC4):c.747T>C(p.Cys249=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDC4	NM_014329.5	c.747T>C	p.Cys249=	synonymous_variant	6/29	ENST00000358933.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDC4	ENST00000358933.10	c.747T>C	p.Cys249=	synonymous_variant	6/29	1	NM_014329.5	P1

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

GnomAD3 exomes AF: 0.230 AC: 57725 AN: 251382 Hom.: 8699 AF XY: 0.219 AC XY: 29793 AN XY: 135852

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 SAS exome AF: 0.260

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

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0731

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.209

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

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0715

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.284

Alfa AF: 0.197 Hom.: 9190

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	7.4
Dann	Benign	0.45
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8

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

Publications

LitVar

Other links and lift over

dbSNP: rs8060686; hg19: chr16-67911517; COSMIC: COSV62765921; COSMIC: COSV62765921;