chr11-128519496-C-T

Variant names:

• chr11-128519496-C-T
• rs11819995
• NM_001143820.2:c.215-28920G>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.215-28920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,182 control chromosomes in the GnomAD database, including 3,991 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 0.23 (3991 hom., cov: 33)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 15 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 (AFR) allele frequency at 95% confidence interval = 0.261 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	NM_001143820.2	MANE Select	c.215-28920G>A		intron	N/A	NP_001137292.1
	ETS1	NM_005238.4		c.82+2417G>A		intron	N/A	NP_005229.1
	ETS1	NM_001330451.2		c.82+2417G>A		intron	N/A	NP_001317380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	ENST00000392668.8	TSL:1 MANE Select	c.215-28920G>A		intron	N/A	ENSP00000376436.3
	ETS1	ENST00000319397.7	TSL:1	c.82+2417G>A		intron	N/A	ENSP00000324578.5
	ETS1	ENST00000531611.5	TSL:1	c.82+2417G>A		intron	N/A	ENSP00000435666.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34547 AN: 152064 Hom.: 3979 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.227 AC: 34575 AN: 152182 Hom.: 3991 Cov.: 33 AF XY: 0.222 AC XY: 16551 AN XY: 74416

African (AFR) AF: 0.265 AC: 10986 AN: 41498

American (AMR) AF: 0.205 AC: 3131 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1047 AN: 5180

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1733 AN: 10584

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14919 AN: 68006

Other (OTH) AF: 0.251 AC: 531 AN: 2112

Alfa AF: 0.226 Hom.: 12684

Bravo AF: 0.232

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.043
DANN	Benign	0.83
PhyloP100		-4.0
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: rs11819995; hg19: chr11-128389391;