11-128522042-C-T

Variant names:

• chr11-128522042-C-T
• rs61907765
• ENST00000319397.7:c.-48G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000319397.7(ETS1):​c.-48G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,526,580 control chromosomes in the GnomAD database, including 30,369 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 0.15 (2375 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27994 hom.)
• Consequence: ETS1 ENST00000319397.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 28 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=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.215-31466G>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.215-31466G>A		intron_variant	Intron 3 of 9	1	NM_001143820.2	ENSP00000376436.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23307 AN: 152064 Hom.: 2377 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.175 AC: 34399 AN: 197096 AF XY: 0.177

Gnomad AFR exome AF: 0.0357

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.00328

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.219

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.195 AC: 267426 AN: 1374398 Hom.: 27994 Cov.: 32 AF XY: 0.193 AC XY: 131303 AN XY: 679760

African (AFR) AF: 0.0282 AC: 825 AN: 29282

American (AMR) AF: 0.179 AC: 6319 AN: 35312

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 4987 AN: 23510

East Asian (EAS) AF: 0.00569 AC: 196 AN: 34438

South Asian (SAS) AF: 0.0937 AC: 7322 AN: 78176

European-Finnish (FIN) AF: 0.230 AC: 11692 AN: 50880

Middle Eastern (MID) AF: 0.146 AC: 781 AN: 5342

European-Non Finnish (NFE) AF: 0.212 AC: 225265 AN: 1061648

Other (OTH) AF: 0.180 AC: 10039 AN: 55810

GnomAD4 genome AF: 0.153 AC: 23294 AN: 152182 Hom.: 2375 Cov.: 32 AF XY: 0.152 AC XY: 11293 AN XY: 74404

African (AFR) AF: 0.0376 AC: 1560 AN: 41528

American (AMR) AF: 0.174 AC: 2667 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 698 AN: 3462

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5188

South Asian (SAS) AF: 0.0881 AC: 425 AN: 4822

European-Finnish (FIN) AF: 0.229 AC: 2427 AN: 10594

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14750 AN: 67972

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.197 Hom.: 731

Bravo AF: 0.147

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		-0.056
PromoterAI		-0.021	Neutral
Mutation Taster		=300/0	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: rs61907765; hg19: chr11-128391937; COSMIC: COSV60092503; COSMIC: COSV60092503;