11-128480393-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.332

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1059 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETS1	NM_001143820.2	c.921C>T	p.Arg307=	synonymous_variant	8/10	ENST00000392668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETS1	ENST00000392668.8	c.921C>T	p.Arg307=	synonymous_variant	8/10	1	NM_001143820.2

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1059 AN: 152098 Hom.: 9 Cov.: 31

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.: 7 AF XY: 0.00753 AC XY: 1021 AN XY: 135602

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.: 81 Cov.: 33 AF XY: 0.00979 AC XY: 7123 AN XY: 727228

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.: 9 Cov.: 31 AF XY: 0.00619 AC XY: 461 AN XY: 74424

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.: 10

Bravo AF: 0.00592

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00932

EpiControl AF: 0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs118149282; hg19: chr11-128350288;