Genetic Variant NM_007265.3:c.1901A>G (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

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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