10-73152312-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_007265.3(ECD):āc.893A>Gā(p.His298Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000614 in 1,613,462 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00041 ( 0 hom., cov: 31)
Exomes š: 0.00063 ( 2 hom. )
Consequence
ECD
NM_007265.3 missense
NM_007265.3 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 5.08
Genes affected
ECD (HGNC:17029): (ecdysoneless cell cycle regulator) Enables histone acetyltransferase binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.24318728).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ECD | NM_007265.3 | c.893A>G | p.His298Arg | missense_variant | 7/14 | ENST00000372979.9 | |
ECD | NM_001135752.1 | c.893A>G | p.His298Arg | missense_variant | 7/15 | ||
ECD | NM_001135753.1 | c.783+1944A>G | intron_variant | ||||
ECD | NR_024203.1 | n.725A>G | non_coding_transcript_exon_variant | 5/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ECD | ENST00000372979.9 | c.893A>G | p.His298Arg | missense_variant | 7/14 | 1 | NM_007265.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000414 AC: 63AN: 152222Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
63
AN:
152222
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000298 AC: 75AN: 251266Hom.: 0 AF XY: 0.000295 AC XY: 40AN XY: 135788
GnomAD3 exomes
AF:
AC:
75
AN:
251266
Hom.:
AF XY:
AC XY:
40
AN XY:
135788
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000634 AC: 927AN: 1461122Hom.: 2 Cov.: 30 AF XY: 0.000581 AC XY: 422AN XY: 726836
GnomAD4 exome
AF:
AC:
927
AN:
1461122
Hom.:
Cov.:
30
AF XY:
AC XY:
422
AN XY:
726836
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000414 AC: 63AN: 152340Hom.: 0 Cov.: 31 AF XY: 0.000336 AC XY: 25AN XY: 74492
GnomAD4 genome
AF:
AC:
63
AN:
152340
Hom.:
Cov.:
31
AF XY:
AC XY:
25
AN XY:
74492
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
7
ExAC
AF:
AC:
29
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 01, 2021 | The c.893A>G (p.H298R) alteration is located in exon 7 (coding exon 6) of the ECD gene. This alteration results from a A to G substitution at nucleotide position 893, causing the histidine (H) at amino acid position 298 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
0.48
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at