11-128519496-C-T

Position:

• chr11-128519496-C-T

Variant summary

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

The ENST00000392668.8(ETS1):​c.215-28920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,182 control chromosomes in the GnomAD database, including 3,991 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 0.23 (3991 hom., cov: 33)
• Consequence: ETS1 ENST00000392668.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.215-28920G>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.215-28920G>A		intron_variant		1	NM_001143820.2	ENSP00000376436

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34547 AN: 152064 Hom.: 3979 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34575 AN: 152182 Hom.: 3991 Cov.: 33 AF XY: 0.222 AC XY: 16551 AN XY: 74416

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.251

Alfa AF: 0.223 Hom.: 8149

Bravo AF: 0.232

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.043
DANN	Benign	0.83

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: rs11819995; hg19: chr11-128389391;