Variant chr6-138876472-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 15/24 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). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 -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/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3 link	c.1579G>A	p.Glu527Lys	missense_variant, splice_region_variant	14/22	ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

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

GnomAD3 exomes

AF:

0.278

AC:

68791

AN:

247542

Hom.:

10453

AF XY:

0.289

AC XY:

38810

AN XY:

134316

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 SAS exome

AF:

0.405

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

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.142

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.296

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.291

GnomAD4 genome

AF:

0.259

AC:

39330

AN:

151954

Hom.:

5365

Cov.:

AF XY:

0.256

AC XY:

19041

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.291

Hom.:

10086

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

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

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

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

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

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