11-128522042-C-T

Position:

• chr11-128522042-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392668.8(ETS1):​c.215-31466G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,526,580 control chromosomes in the GnomAD database, including 30,369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2375 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27994 hom.)
• Consequence: ETS1 ENST00000392668.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.215-31466G>A		intron_variant		ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8	c.215-31466G>A		intron_variant		1	NM_001143820.2	ENSP00000376436

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23307 AN: 152064 Hom.: 2377 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.175 AC: 34399 AN: 197096 Hom.: 3498 AF XY: 0.177 AC XY: 19026 AN XY: 107740

Gnomad AFR exome AF: 0.0357

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.00328

Gnomad SAS exome AF: 0.0925

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.195 AC: 267426 AN: 1374398 Hom.: 27994 Cov.: 32 AF XY: 0.193 AC XY: 131303 AN XY: 679760

Gnomad4 AFR exome AF: 0.0282

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.00569

Gnomad4 SAS exome AF: 0.0937

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.153 AC: 23294 AN: 152182 Hom.: 2375 Cov.: 32 AF XY: 0.152 AC XY: 11293 AN XY: 74404

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.0881

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.165

Alfa AF: 0.197 Hom.: 731

Bravo AF: 0.147

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs61907765; hg19: chr11-128391937; COSMIC: COSV60092503; COSMIC: COSV60092503;