NM_001143820.2:c.69+6004G>A

Variant names:

• chr11-128567058-C-T
• rs7117932
• NM_001143820.2:c.69+6004G>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.69+6004G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,056 control chromosomes in the GnomAD database, including 11,129 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 0.37 (11129 hom., cov: 32)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 14 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)

ENSG00000308547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.69+6004G>A		intron_variant	Intron 2 of 9	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8	c.69+6004G>A		intron_variant	Intron 2 of 9	1	NM_001143820.2	ENSP00000376436.3
ETS1	ENST00000525404.5	n.138+6004G>A		intron_variant	Intron 2 of 3	2
ENSG00000308547	ENST00000834937.1	n.717+602C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56223 AN: 151938 Hom.: 11141 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.370 AC: 56208 AN: 152056 Hom.: 11129 Cov.: 32 AF XY: 0.368 AC XY: 27372 AN XY: 74316

African (AFR) AF: 0.248 AC: 10306 AN: 41498

American (AMR) AF: 0.326 AC: 4976 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3466

East Asian (EAS) AF: 0.234 AC: 1210 AN: 5180

South Asian (SAS) AF: 0.385 AC: 1856 AN: 4818

European-Finnish (FIN) AF: 0.435 AC: 4599 AN: 10574

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30237 AN: 67940

Other (OTH) AF: 0.360 AC: 759 AN: 2108

Alfa AF: 0.412 Hom.: 35719

Bravo AF: 0.353

Asia WGS AF: 0.275 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		1.1
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: rs7117932; hg19: chr11-128436953;