Variant chr6-138865022-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001077706.3(ECT2L):c.1318T>G(p.Trp440Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,613,460 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.015 ( 41 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 57 hom. )

Consequence

ECT2L
NM_001077706.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.617

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023939908).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (2290/152342) while in subpopulation AFR AF= 0.0476 (1979/41586). AF 95% confidence interval is 0.0458. There are 41 homozygotes in gnomad4. There are 1121 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3 linkuse as main transcript	c.1318T>G	p.Trp440Gly	missense_variant	12/22	ENST00000541398.7	NP_001071174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ECT2L	ENST00000541398.7 linkuse as main transcript	c.1318T>G	p.Trp440Gly	missense_variant	12/22	5	NM_001077706.3	ENSP00000442307	P1
ECT2L	ENST00000367682.6 linkuse as main transcript	c.1318T>G	p.Trp440Gly	missense_variant	11/21	5		ENSP00000356655	P1
ECT2L	ENST00000495970.1 linkuse as main transcript	n.306T>G		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2288

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00528

AC:

1317

AN:

249278

Hom.:

AF XY:

0.00452

AC XY:

611

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.0493

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00810

GnomAD4 exome

AF:

0.00271

AC:

3965

AN:

1461118

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1841

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00812

Gnomad4 ASJ exome

AF:

0.00360

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.00698

GnomAD4 genome

AF:

0.0150

AC:

2290

AN:

152342

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1121

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0476

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.0178

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0462

AC:

172

ESP6500EA

AF:

0.00110

AC:

ExAC

AF:

0.00616

AC:

744

EpiCase

AF:

0.00245

EpiControl

AF:

0.00231

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

DANN

Benign

0.55

DEOGEN2

Benign

0.0026

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.26

.;.;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.11

Sift

Benign

0.36

T;T;.

Sift4G

Benign

0.38

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.14

MVP

0.19

MPC

0.15

ClinPred

0.0068

GERP RS

-6.0

Varity_R

0.062

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over