dbSNP rs3812619: ECD:p.Arg45Gln (chr10-73163804-C-T) – 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.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 1,613,782 control chromosomes in the GnomAD database, including 12,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 3139 hom., cov: 32)

Exomes 𝑓: 0.090 ( 9275 hom. )

Consequence

ECD
NM_007265.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

32 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=0.0035088956).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECD	NM_007265.3 link	c.134G>A	p.Arg45Gln	missense_variant	Exon 2 of 14	ENST00000372979.9	NP_009196.1	O95905-1
ECD	NM_001135752.1 link	c.134G>A	p.Arg45Gln	missense_variant	Exon 2 of 15		NP_001129224.1	O95905-3
ECD	NM_001135753.1 link	c.134G>A	p.Arg45Gln	missense_variant	Exon 2 of 13		NP_001129225.1	O95905-2
ECD	NR_024203.1 link	n.231-3253G>A		intron_variant	Intron 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECD	ENST00000372979.9 link	c.134G>A	p.Arg45Gln	missense_variant	Exon 2 of 14	1	NM_007265.3	ENSP00000362070.4		O95905-1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23873

AN:

151888

Hom.:

3114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.0423

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0653

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.126

AC:

31788

AN:

251458

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.0945

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.0459

Gnomad NFE exome

AF:

0.0658

Gnomad OTH exome

AF:

0.0938

GnomAD4 exome

AF:

0.0896

AC:

131028

AN:

1461774

Hom.:

9275

Cov.:

AF XY:

0.0927

AC XY:

67407

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.346

AC:

11589

AN:

33476

American (AMR)

AF:

0.0959

AC:

4291

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3242

AN:

26134

East Asian (EAS)

AF:

0.281

AC:

11148

AN:

39686

South Asian (SAS)

AF:

0.224

AC:

19312

AN:

86242

European-Finnish (FIN)

AF:

0.0472

AC:

2520

AN:

53418

Middle Eastern (MID)

AF:

0.0928

AC:

535

AN:

5768

European-Non Finnish (NFE)

AF:

0.0645

AC:

71734

AN:

1111938

Other (OTH)

AF:

0.110

AC:

6657

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

6045

12091

18136

24182

30227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.158

AC:

23950

AN:

152008

Hom.:

3139

Cov.:

AF XY:

0.158

AC XY:

11745

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.336

AC:

13911

AN:

41408

American (AMR)

AF:

0.106

AC:

1624

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

440

AN:

3468

East Asian (EAS)

AF:

0.306

AC:

1577

AN:

5162

South Asian (SAS)

AF:

0.232

AC:

1116

AN:

4814

European-Finnish (FIN)

AF:

0.0423

AC:

448

AN:

10592

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0654

AC:

4443

AN:

67976

Other (OTH)

AF:

0.128

AC:

270

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

891

1781

2672

3562

4453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.103

Hom.:

4652

Bravo

AF:

0.168

TwinsUK

AF:

0.0583

AC:

216

ALSPAC

AF:

0.0615

AC:

237

ESP6500AA

AF:

0.325

AC:

1433

ESP6500EA

AF:

0.0717

AC:

617

ExAC

AF:

0.134

AC:

16203

Asia WGS

AF:

0.270

AC:

937

AN:

3478

EpiCase

AF:

0.0657

EpiControl

AF:

0.0653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.018

T;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.21

T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-0.89

PhyloP100

1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

0.57

N;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.98

T;T;T;T

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.052

MPC

0.092

ClinPred

0.0023

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.014

gMVP

0.19

Mutation Taster

=97/3

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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rs3812619

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