chr11-128576292-G-A

Variant names:

• chr11-128576292-G-A
• rs7126621
• NM_001143820.2:c.-14-3148C>T

Variant summary

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

The NM_001143820.2(ETS1):​c.-14-3148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,098 control chromosomes in the GnomAD database, including 13,702 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 0.42 (13702 hom., cov: 32)
• Consequence: ETS1 NM_001143820.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 8 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.-14-3148C>T		intron_variant	Intron 1 of 9	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8	c.-14-3148C>T		intron_variant	Intron 1 of 9	1	NM_001143820.2	ENSP00000376436.3
ETS1	ENST00000525404.5	n.56-3148C>T		intron_variant	Intron 1 of 3	2
ETS1	ENST00000527676.2	n.39-3148C>T		intron_variant	Intron 1 of 2	5
ENSG00000308547	ENST00000834937.1	n.718-6705G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63667 AN: 151980 Hom.: 13705 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.419 AC: 63665 AN: 152098 Hom.: 13702 Cov.: 32 AF XY: 0.416 AC XY: 30964 AN XY: 74354

African (AFR) AF: 0.381 AC: 15781 AN: 41472

American (AMR) AF: 0.354 AC: 5414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1690 AN: 3466

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5180

South Asian (SAS) AF: 0.402 AC: 1941 AN: 4830

European-Finnish (FIN) AF: 0.446 AC: 4710 AN: 10562

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31552 AN: 67980

Other (OTH) AF: 0.385 AC: 813 AN: 2110

Alfa AF: 0.450 Hom.: 9736

Bravo AF: 0.408

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.8
DANN	Benign	0.89
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: rs7126621; hg19: chr11-128446187;