rs12223943

Variant names:

• chr11-128525733-G-T
• rs12223943
• NM_001143820.2:c.214+30558C>A

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+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
• Publications: 8 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=-0.85).
• 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 rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.214+30558C>A		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+30558C>A		intron_variant	Intron 3 of 9	1	NM_001143820.2	ENSP00000376436.3

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

African (AFR) AF: 0.0151 AC: 626 AN: 41336

American (AMR) AF: 0.0486 AC: 740 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0799 AC: 277 AN: 3466

East Asian (EAS) AF: 0.146 AC: 754 AN: 5158

South Asian (SAS) AF: 0.106 AC: 509 AN: 4802

European-Finnish (FIN) AF: 0.0873 AC: 906 AN: 10382

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0679 AC: 4611 AN: 67936

Other (OTH) AF: 0.0674 AC: 141 AN: 2092

Alfa AF: 0.0663 Hom.: 175

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
PhyloP100		0.31
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: rs12223943; hg19: chr11-128395628; COSMIC: COSV107401140; COSMIC: COSV107401140;