rs12223943

Positions:

• chr11-128525733-G-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+30558C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0569 in 151,596 control chromosomes in the GnomAD database, including 338 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 0.057 (338 hom., cov: 30)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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 (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETS1	NM_001143820.2	c.214+30558C>A		intron_variant		ENST00000392668.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETS1	ENST00000392668.8	c.214+30558C>A		intron_variant		1	NM_001143820.2

Frequencies

GnomAD3 genomes AF: 0.0569 AC: 8627 AN: 151500 Hom.: 338 Cov.: 30

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0569 AC: 8622 AN: 151596 Hom.: 338 Cov.: 30 AF XY: 0.0590 AC XY: 4368 AN XY: 74042

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0873

Gnomad4 NFE AF: 0.0679

Gnomad4 OTH AF: 0.0674

Alfa AF: 0.0657 Hom.: 159

Bravo AF: 0.0518

Asia WGS AF: 0.105 AC: 363 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	1.6
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12223943; hg19: chr11-128395628;