Variant rs587777938 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PVS1_ModeratePP3BS1_SupportingBS2

The NM_001077706.3(ECT2L):c.1579-1G>C variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00117 in 1,608,184 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 12 hom. )

Consequence

ECT2L
NM_001077706.3 splice_acceptor, intron

Scores

Splicing: ADA: 0.9999

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.78

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 Likely_benign. Variant got -2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.031675875 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, BayesDel_noAF, MutationTaster was below the threshold]

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00639 (973/152208) while in subpopulation AFR AF= 0.0213 (886/41526). AF 95% confidence interval is 0.0202. There are 8 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 32. 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 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECT2L	NM_001077706.3 linkuse as main transcript	c.1579-1G>C		splice_acceptor_variant, intron_variant		ENST00000541398.7	NP_001071174.1	Q008S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECT2L	ENST00000541398.7 linkuse as main transcript	c.1579-1G>C		splice_acceptor_variant, intron_variant		5	NM_001077706.3	ENSP00000442307.2		Q008S8
ECT2L	ENST00000367682.6 linkuse as main transcript	c.1579-1G>C		splice_acceptor_variant, intron_variant		5		ENSP00000356655.2		Q008S8

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

973

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00152

AC:

378

AN:

247898

Hom.:

AF XY:

0.00109

AC XY:

147

AN XY:

134518

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.000910

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000619

AC:

901

AN:

1455976

Hom.:

Cov.:

AF XY:

0.000501

AC XY:

363

AN XY:

724550

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000172

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00639

AC:

973

AN:

152208

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

471

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00762

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00199

AC:

241

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000594

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

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Pathogenic

0.83

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

GERP RS

5.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.96

SpliceAI score (max)

0.66

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.66

Position offset: 1

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