11-128511079-C-T

Variant names:

• chr11-128511079-C-T
• rs11221332
• NM_001143820.2:c.215-20503G>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.215-20503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,100 control chromosomes in the GnomAD database, including 2,791 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 0.18 (2791 hom., cov: 32)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 47 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 (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.215-20503G>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.215-20503G>A		intron_variant	Intron 3 of 9	1	NM_001143820.2	ENSP00000376436.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27282 AN: 151982 Hom.: 2795 Cov.: 32

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0483

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.179 AC: 27278 AN: 152100 Hom.: 2791 Cov.: 32 AF XY: 0.180 AC XY: 13391 AN XY: 74344

African (AFR) AF: 0.0928 AC: 3852 AN: 41492

American (AMR) AF: 0.184 AC: 2811 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3466

East Asian (EAS) AF: 0.0483 AC: 250 AN: 5180

South Asian (SAS) AF: 0.239 AC: 1155 AN: 4826

European-Finnish (FIN) AF: 0.229 AC: 2419 AN: 10570

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15138 AN: 67956

Other (OTH) AF: 0.185 AC: 391 AN: 2110

Alfa AF: 0.207 Hom.: 12480

Bravo AF: 0.171

Asia WGS AF: 0.168 AC: 582 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	0.36
DANN	Benign	0.64
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11221332; hg19: chr11-128380974;