dbSNP rs1529151: ECT2L:p.Glu527Lys (chr6-138876472-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001077706.3(ECT2L):c.1579G>A(p.Glu527Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,604,820 control chromosomes in the GnomAD database, including 72,264 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5365 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66899 hom. )

Consequence

ECT2L
NM_001077706.3 missense, splice_region

Scores

Splicing: ADA: 0.008845

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.67

Publications

24 publications found

Variant links:

Genes affected

ECT2L (HGNC:21118): (epithelial cell transforming 2 like) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ECT2L 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=0.0022402406).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3 link	c.1579G>A	p.Glu527Lys	missense_variant, splice_region_variant	Exon 14 of 22	ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7 link	c.1579G>A	p.Glu527Lys	missense_variant, splice_region_variant	Exon 14 of 22	5	NM_001077706.3	ENSP00000442307.2		Q008S8
ECT2L	ENST00000367682.6 link	c.1579G>A	p.Glu527Lys	missense_variant, splice_region_variant	Exon 13 of 21	5		ENSP00000356655.2		Q008S8

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39335

AN:

151834

Hom.:

5367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.253

GnomAD2 exomes

AF:

0.278

AC:

68791

AN:

247542

AF XY:

0.289

show subpopulations

Gnomad AFR exome

AF:

0.199

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.299

AC:

433977

AN:

1452866

Hom.:

66899

Cov.:

AF XY:

0.303

AC XY:

218793

AN XY:

723112

show subpopulations

African (AFR)

AF:

0.199

AC:

6630

AN:

33242

American (AMR)

AF:

0.142

AC:

6301

AN:

44326

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

7258

AN:

26048

East Asian (EAS)

AF:

0.296

AC:

11712

AN:

39622

South Asian (SAS)

AF:

0.399

AC:

34207

AN:

85684

European-Finnish (FIN)

AF:

0.237

AC:

12667

AN:

53350

Middle Eastern (MID)

AF:

0.275

AC:

1580

AN:

5748

European-Non Finnish (NFE)

AF:

0.304

AC:

336118

AN:

1104794

Other (OTH)

AF:

0.291

AC:

17504

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

12753

25505

38258

51010

63763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11056

22112

33168

44224

55280

<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:

0.259

AC:

39330

AN:

151954

Hom.:

5365

Cov.:

AF XY:

0.256

AC XY:

19041

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.197

AC:

8166

AN:

41436

American (AMR)

AF:

0.207

AC:

3163

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

962

AN:

3462

East Asian (EAS)

AF:

0.308

AC:

1592

AN:

5170

South Asian (SAS)

AF:

0.395

AC:

1906

AN:

4824

European-Finnish (FIN)

AF:

0.229

AC:

2409

AN:

10538

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20237

AN:

67948

Other (OTH)

AF:

0.249

AC:

524

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1497

2995

4492

5990

7487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.286

Hom.:

13724

Bravo

AF:

0.249

TwinsUK

AF:

0.304

AC:

1126

ALSPAC

AF:

0.308

AC:

1188

ESP6500AA

AF:

0.197

AC:

733

ESP6500EA

AF:

0.299

AC:

2448

ExAC

AF:

0.287

AC:

34634

Asia WGS

AF:

0.311

AC:

1085

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.291

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0023

T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.61

.;.;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L

PhyloP100

1.7

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.049

Sift

Benign

0.37

T;T;.

Sift4G

Benign

0.79

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.039

MPC

0.098

ClinPred

0.0047

GERP RS

3.5

Varity_R

0.043

gMVP

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0088

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.47

Position offset: 0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over