Variant chr11-128480393-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000531611.5(ETS1):c.781+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 1,614,070 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0097 ( 81 hom. )

Consequence

ETS1
ENST00000531611.5 splice_region, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.332

Variant links:

Genes affected

ETS1 (HGNC:3488): (ETS proto-oncogene 1, transcription factor) This gene encodes a member of the ETS family of transcription factors, which are defined by the presence of a conserved ETS DNA-binding domain that recognizes the core consensus DNA sequence GGAA/T in target genes. These proteins function either as transcriptional activators or repressors of numerous genes, and are involved in stem cell development, cell senescence and death, and tumorigenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ETS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 11-128480393-G-A is Benign according to our data. Variant chr11-128480393-G-A is described in ClinVar as [Benign]. Clinvar id is 715411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1058 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2 linkuse as main transcript	c.921C>T	p.Arg307=	synonymous_variant	8/10	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8 linkuse as main transcript	c.921C>T	p.Arg307=	synonymous_variant	8/10	1	NM_001143820.2	ENSP00000376436		P14921-3

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

1059

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00837

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00685

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00718

AC:

1802

AN:

250942

Hom.:

AF XY:

0.00753

AC XY:

1021

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00785

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00735

Gnomad FIN exome

AF:

0.00365

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00972

AC:

14214

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00979

AC XY:

7123

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00402

Gnomad4 ASJ exome

AF:

0.00891

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00784

Gnomad4 FIN exome

AF:

0.00447

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00876

GnomAD4 genome

AF:

0.00695

AC:

1058

AN:

152216

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00837

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00592

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00932

EpiControl

AF:

0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ETS1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.8

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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