dbSNP rs76700722: ECT2L:p.Ile146Thr (chr6-138843073-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001077706.3(ECT2L):c.437T>C(p.Ile146Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00216 in 1,613,916 control chromosomes in the GnomAD database, including 75 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 0.012 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 36 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 6.10

Publications

2 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052326918).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1782/152292) while in subpopulation AFR AF = 0.0404 (1678/41572). AF 95% confidence interval is 0.0388. There are 39 homozygotes in GnomAd4. There are 849 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ECT2L	NM_001077706.3 link	c.437T>C	p.Ile146Thr	missense_variant	Exon 6 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.437T>C	p.Ile146Thr	missense_variant	Exon 6 of 22	5	NM_001077706.3	ENSP00000442307.2		Q008S8
ECT2L	ENST00000367682.6 link	c.437T>C	p.Ile146Thr	missense_variant	Exon 5 of 21	5		ENSP00000356655.2		Q008S8

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1772

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00284

AC:

709

AN:

249492

AF XY:

0.00236

show subpopulations

Gnomad AFR exome

AF:

0.0409

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00117

AC:

1705

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

753

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.0421

AC:

1410

AN:

33478

American (AMR)

AF:

0.00165

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000197

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111858

Other (OTH)

AF:

0.00280

AC:

169

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

182

272

363

454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.0117

AC:

1782

AN:

152292

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

849

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0404

AC:

1678

AN:

41572

American (AMR)

AF:

0.00451

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68016

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

144

217

289

361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00449

Hom.:

Bravo

AF:

0.0138

ESP6500AA

AF:

0.0353

AC:

140

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00345

AC:

417

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

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

0.25

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;T;T

Eigen

Benign

-0.057

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

.;.;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M;M

PhyloP100

6.1

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-4.0

D;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.36

B;B;B

Vest4

0.61

MVP

0.43

MPC

0.30

ClinPred

0.050

GERP RS

5.7

Varity_R

0.39

gMVP

0.39

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over