11-128546047-A-T

Variant names:

• chr11-128546047-A-T
• rs4129229
• NM_001143820.2:c.214+10244T>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+10244T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,108 control chromosomes in the GnomAD database, including 5,359 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 0.24 (5359 hom., cov: 32)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.214+10244T>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+10244T>A		intron_variant	Intron 3 of 9	1	NM_001143820.2	ENSP00000376436.3
ETS1	ENST00000525404.5	n.284-9264T>A		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36061 AN: 151990 Hom.: 5366 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.237 AC: 36047 AN: 152108 Hom.: 5359 Cov.: 32 AF XY: 0.235 AC XY: 17494 AN XY: 74354

African (AFR) AF: 0.0735 AC: 3052 AN: 41516

American (AMR) AF: 0.257 AC: 3932 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3470

East Asian (EAS) AF: 0.139 AC: 722 AN: 5180

South Asian (SAS) AF: 0.200 AC: 966 AN: 4824

European-Finnish (FIN) AF: 0.314 AC: 3316 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22146 AN: 67952

Other (OTH) AF: 0.227 AC: 479 AN: 2112

Alfa AF: 0.164 Hom.: 423

Bravo AF: 0.225

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		0.12
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: rs4129229; hg19: chr11-128415942;