dbSNP rs6495119: EDC3:c.821-1480A>G (chr15-74642099-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025083.5(EDC3):c.821-1480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,164 control chromosomes in the GnomAD database, including 3,549 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 0.18 ( 3549 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

EDC3
NM_025083.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Publications

11 publications found

Variant links:

Genes affected

EDC3 (HGNC:26114): (enhancer of mRNA decapping 3) This gene encodes a protein that is important in mRNA degradation. The encoded protein is a component of a decapping complex that promotes efficient removal of the monomethylguanosine (m7G) cap from mRNAs, as part of the 5' to 3' mRNA decay pathway. Mutations in this gene have been identified in human patients with an autosomal recessive form of intellectual disability. [provided by RefSeq, May 2017]

EDC3 links:

CLK3 (HGNC:2071): (CDC like kinase 3) This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9. [provided by RefSeq, Jul 2008]

CLK3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025083.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDC3	NM_025083.5	MANE Select	c.821-1480A>G	intron	N/A	NP_079359.2
EDC3	NM_001142443.3		c.821-1480A>G	intron	N/A	NP_001135915.1	Q96F86
EDC3	NM_001142444.3		c.821-1480A>G	intron	N/A	NP_001135916.1	Q96F86

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDC3	ENST00000315127.9	TSL:1 MANE Select	c.821-1480A>G	intron	N/A	ENSP00000320503.4	Q96F86
EDC3	ENST00000426797.7	TSL:1	c.821-1480A>G	intron	N/A	ENSP00000401343.3	Q96F86
EDC3	ENST00000568176.5	TSL:1	c.821-1480A>G	intron	N/A	ENSP00000455580.1	Q96F86

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27279

AN:

152038

Hom.:

3523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0784

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.180

AC:

27363

AN:

152156

Hom.:

3549

Cov.:

AF XY:

0.187

AC XY:

13917

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.276

AC:

11445

AN:

41478

American (AMR)

AF:

0.320

AC:

4895

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

290

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2149

AN:

5162

South Asian (SAS)

AF:

0.310

AC:

1496

AN:

4824

European-Finnish (FIN)

AF:

0.117

AC:

1241

AN:

10592

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0784

AC:

5333

AN:

68026

Other (OTH)

AF:

0.185

AC:

390

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1035

2070

3105

4140

5175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

2825

Bravo

AF:

0.197

Asia WGS

AF:

0.422

AC:

1462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.13

(source)

DANN

Benign

0.72

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over