11-128540941-C-T

Variant names:

• chr11-128540941-C-T
• rs3809006
• NM_001143820.2:c.214+15350G>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+15350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,988 control chromosomes in the GnomAD database, including 26,809 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 0.59 (26809 hom., cov: 31)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 12 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143820.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	NM_001143820.2	MANE Select	c.214+15350G>A		intron	N/A	NP_001137292.1	P14921-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	ENST00000392668.8	TSL:1 MANE Select	c.214+15350G>A		intron	N/A	ENSP00000376436.3	P14921-3
	ETS1	ENST00000900294.1		c.214+15350G>A		intron	N/A	ENSP00000570353.1
	ETS1	ENST00000917573.1		c.214+15350G>A		intron	N/A	ENSP00000587632.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89335 AN: 151870 Hom.: 26777 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.588 AC: 89419 AN: 151988 Hom.: 26809 Cov.: 31 AF XY: 0.598 AC XY: 44414 AN XY: 74296

African (AFR) AF: 0.649 AC: 26911 AN: 41454

American (AMR) AF: 0.632 AC: 9660 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3472

East Asian (EAS) AF: 0.817 AC: 4227 AN: 5172

South Asian (SAS) AF: 0.738 AC: 3555 AN: 4816

European-Finnish (FIN) AF: 0.572 AC: 6037 AN: 10560

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35650 AN: 67934

Other (OTH) AF: 0.560 AC: 1177 AN: 2102

Alfa AF: 0.563 Hom.: 3517

Bravo AF: 0.589

Asia WGS AF: 0.746 AC: 2592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.46
DANN	Benign	0.81
PhyloP100		-0.88
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: rs3809006; hg19: chr11-128410836;