Genetic Variant ECD:p.Asp634Gly (chr10-73134617-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_007265.3(ECD):c.1901A>G(p.Asp634Gly) variant causes a missense change. The variant allele was found at a frequency of 0.083 in 1,614,064 control chromosomes in the GnomAD database, including 8,384 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 0.10 ( 1238 hom., cov: 32)

Exomes 𝑓: 0.081 ( 7146 hom. )

Consequence

ECD
NM_007265.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.68

Publications

41 publications found

Variant links:

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]

ECD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0017505586).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECD	NM_007265.3 link	c.1901A>G	p.Asp634Gly	missense_variant	Exon 14 of 14	ENST00000372979.9	NP_009196.1	O95905-1
ECD	NM_001135752.1 link	c.2000A>G	p.Asp667Gly	missense_variant	Exon 15 of 15		NP_001129224.1	O95905-3
ECD	NM_001135753.1 link	c.1772A>G	p.Asp591Gly	missense_variant	Exon 13 of 13		NP_001129225.1	O95905-2
ECD	NR_024203.1 link	n.1733A>G		non_coding_transcript_exon_variant	Exon 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECD	ENST00000372979.9 link	c.1901A>G	p.Asp634Gly	missense_variant	Exon 14 of 14	1	NM_007265.3	ENSP00000362070.4		O95905-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15923

AN:

152140

Hom.:

1218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0882

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.0411

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0607

Gnomad OTH

AF:

0.0938

GnomAD2 exomes

AF:

0.110

AC:

27648

AN:

251416

AF XY:

0.113

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.0857

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.0437

Gnomad NFE exome

AF:

0.0609

Gnomad OTH exome

AF:

0.0851

GnomAD4 exome

AF:

0.0807

AC:

117965

AN:

1461806

Hom.:

7146

Cov.:

AF XY:

0.0846

AC XY:

61522

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.165

AC:

5537

AN:

33474

American (AMR)

AF:

0.0867

AC:

3878

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2900

AN:

26136

East Asian (EAS)

AF:

0.280

AC:

11119

AN:

39698

South Asian (SAS)

AF:

0.222

AC:

19135

AN:

86244

European-Finnish (FIN)

AF:

0.0451

AC:

2407

AN:

53420

Middle Eastern (MID)

AF:

0.0751

AC:

433

AN:

5766

European-Non Finnish (NFE)

AF:

0.0602

AC:

66917

AN:

1111956

Other (OTH)

AF:

0.0934

AC:

5639

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5325

10651

15976

21302

26627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2864

5728

8592

11456

14320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.105

AC:

15983

AN:

152258

Hom.:

1238

Cov.:

AF XY:

0.107

AC XY:

7985

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.161

AC:

6686

AN:

41546

American (AMR)

AF:

0.0882

AC:

1349

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

389

AN:

3470

East Asian (EAS)

AF:

0.304

AC:

1574

AN:

5184

South Asian (SAS)

AF:

0.230

AC:

1109

AN:

4822

European-Finnish (FIN)

AF:

0.0411

AC:

436

AN:

10616

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0608

AC:

4132

AN:

68014

Other (OTH)

AF:

0.0961

AC:

203

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

709

1418

2127

2836

3545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0810

Hom.:

2298

Bravo

AF:

0.108

TwinsUK

AF:

0.0550

AC:

204

ALSPAC

AF:

0.0579

AC:

223

ESP6500AA

AF:

0.151

AC:

665

ESP6500EA

AF:

0.0664

AC:

571

ExAC

AF:

0.114

AC:

13818

Asia WGS

AF:

0.259

AC:

898

AN:

3478

EpiCase

AF:

0.0610

EpiControl

AF:

0.0600

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

6.7

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.27

MPC

0.47

ClinPred

0.011

GERP RS

5.7

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.55

gMVP

0.47

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over