Menu
GeneBe

15-74655734-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_025083.5(EDC3):c.819G>A(p.Thr273=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 1,601,976 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 31)
Exomes 𝑓: 0.00054 ( 6 hom. )

Consequence

EDC3
NM_025083.5 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00003633
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-74655734-C-T is Benign according to our data. Variant chr15-74655734-C-T is described in ClinVar as [Benign]. Clinvar id is 712171.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.19 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000539 (781/1449708) while in subpopulation AFR AF= 0.0163 (542/33180). AF 95% confidence interval is 0.0152. There are 6 homozygotes in gnomad4_exome. There are 362 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EDC3NM_025083.5 linkuse as main transcriptc.819G>A p.Thr273= splice_region_variant, synonymous_variant 4/7 ENST00000315127.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EDC3ENST00000315127.9 linkuse as main transcriptc.819G>A p.Thr273= splice_region_variant, synonymous_variant 4/71 NM_025083.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00446
AC:
678
AN:
152150
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0149
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.00122
AC:
303
AN:
248628
Hom.:
2
AF XY:
0.000841
AC XY:
113
AN XY:
134420
show subpopulations
Gnomad AFR exome
AF:
0.0153
Gnomad AMR exome
AF:
0.000792
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000827
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000890
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000539
AC:
781
AN:
1449708
Hom.:
6
Cov.:
32
AF XY:
0.000504
AC XY:
362
AN XY:
718752
show subpopulations
Gnomad4 AFR exome
AF:
0.0163
Gnomad4 AMR exome
AF:
0.000860
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000991
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000390
Gnomad4 OTH exome
AF:
0.00120
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00448
AC:
682
AN:
152268
Hom.:
2
Cov.:
31
AF XY:
0.00427
AC XY:
318
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0150
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00353
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.000832
Hom.:
0
Bravo
AF:
0.00496
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000594

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
0.078
Dann
Benign
0.83
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000036
dbscSNV1_RF
Benign
0.012
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76943949; hg19: chr15-74948075; API