11-128545234-T-C

Variant names:

• chr11-128545234-T-C
• rs4128561
• NM_001143820.2:c.214+11057A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143820.2(ETS1):​c.214+11057A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,998 control chromosomes in the GnomAD database, including 27,314 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 0.58 (27314 hom., cov: 31)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.214+11057A>G		intron_variant	Intron 3 of 9	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8	c.214+11057A>G		intron_variant	Intron 3 of 9	1	NM_001143820.2	ENSP00000376436.3
ETS1	ENST00000525404.5	n.284-8451A>G		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87528 AN: 151880 Hom.: 27263 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.577 AC: 87643 AN: 151998 Hom.: 27314 Cov.: 31 AF XY: 0.585 AC XY: 43457 AN XY: 74282

African (AFR) AF: 0.798 AC: 33087 AN: 41474

American (AMR) AF: 0.608 AC: 9274 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4252 AN: 5178

South Asian (SAS) AF: 0.642 AC: 3082 AN: 4804

European-Finnish (FIN) AF: 0.501 AC: 5288 AN: 10562

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29643 AN: 67936

Other (OTH) AF: 0.552 AC: 1163 AN: 2106

Alfa AF: 0.476 Hom.: 15272

Bravo AF: 0.595

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.53
DANN	Benign	0.38
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4128561; hg19: chr11-128415129;