dbSNP rs79219465: ECT2L:p.Phe4Leu (chr6-138813286-C-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.12C>A(p.Phe4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,612,132 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.016 ( 75 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 72 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.380

Publications

8 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=0.0022556484).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3 link	c.12C>A	p.Phe4Leu	missense_variant	Exon 3 of 22	ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ECT2L	ENST00000541398.7 link	c.12C>A	p.Phe4Leu	missense_variant	Exon 3 of 22	5	NM_001077706.3	ENSP00000442307.2	Q008S8
ECT2L	ENST00000367682.6 link	c.12C>A	p.Phe4Leu	missense_variant	Exon 2 of 21	5		ENSP00000356655.2	Q008S8
ECT2L	ENST00000401414.4 link	c.12C>A	p.Phe4Leu	missense_variant	Exon 2 of 3	4		ENSP00000385187.3	B7ZBI6

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2451

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00417

AC:

1032

AN:

247542

AF XY:

0.00314

show subpopulations

Gnomad AFR exome

AF:

0.0602

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00216

GnomAD4 exome

AF:

0.00159

AC:

2325

AN:

1459892

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1013

AN XY:

726200

show subpopulations

African (AFR)

AF:

0.0586

AC:

1953

AN:

33314

American (AMR)

AF:

0.00219

AC:

AN:

44204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000701

AC:

AN:

85616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000675

AC:

AN:

1111560

Other (OTH)

AF:

0.00308

AC:

186

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

180

270

360

450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0161

AC:

2453

AN:

152240

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1147

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0553

AC:

2297

AN:

41542

American (AMR)

AF:

0.00667

AC:

102

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68016

Other (OTH)

AF:

0.0156

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

111

222

334

445

556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00632

Hom.:

Bravo

AF:

0.0192

ESP6500AA

AF:

0.0598

AC:

220

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00515

AC:

622

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000415

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

Uncertain

0.51

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0016

T;T;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.49

.;.;T;T

MetaRNN

Benign

0.0023

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L;.

PhyloP100

0.38

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.50

N;N;.;N

REVEL

Benign

0.11

Sift

Benign

0.33

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.23

MutPred

0.13

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.40

MPC

0.10

ClinPred

0.015

GERP RS

0.69

Varity_R

0.058

gMVP

0.16

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over