11-128546047-A-T

Position:

• chr11-128546047-A-T

Variant summary

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

The NM_001143820.2(ETS1):​c.214+10244T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,108 control chromosomes in the GnomAD database, including 5,359 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 0.24 (5359 hom., cov: 32)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.214+10244T>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.214+10244T>A		intron_variant		1	NM_001143820.2	ENSP00000376436
ETS1	ENST00000525404.5	n.284-9264T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36061 AN: 151990 Hom.: 5366 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.237 AC: 36047 AN: 152108 Hom.: 5359 Cov.: 32 AF XY: 0.235 AC XY: 17494 AN XY: 74354

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.227

Alfa AF: 0.164 Hom.: 423

Bravo AF: 0.225

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4129229; hg19: chr11-128415942;