11-128480393-G-A

Variant names:

• chr11-128480393-G-A
• rs118149282
• NM_001143820.2:c.921C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001143820.2(ETS1):​c.921C>T​(p.Arg307Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 1,614,070 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0097 (81 hom.)
• Consequence: ETS1 NM_001143820.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.332
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-128480393-G-A is Benign according to our data. Variant chr11-128480393-G-A is described in ClinVar as [Benign]. Clinvar id is 715411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.332 with no splicing effect.
• BS2: High AC in GnomAd4 at 1058 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.921C>T	p.Arg307Arg	synonymous_variant	Exon 8 of 10	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8	c.921C>T	p.Arg307Arg	synonymous_variant	Exon 8 of 10	1	NM_001143820.2	ENSP00000376436.3

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1059 AN: 152098 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00718 AC: 1802 AN: 250942 AF XY: 0.00753

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00785

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.00669

GnomAD4 exome AF: 0.00972 AC: 14214 AN: 1461854 Hom.: 81 Cov.: 33 AF XY: 0.00979 AC XY: 7123 AN XY: 727228

African (AFR) AF: 0.00125 AC: 42 AN: 33480

American (AMR) AF: 0.00402 AC: 180 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00891 AC: 233 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00784 AC: 676 AN: 86256

European-Finnish (FIN) AF: 0.00447 AC: 239 AN: 53418

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.0111 AC: 12310 AN: 1111980

Other (OTH) AF: 0.00876 AC: 529 AN: 60396

GnomAD4 genome AF: 0.00695 AC: 1058 AN: 152216 Hom.: 9 Cov.: 31 AF XY: 0.00619 AC XY: 461 AN XY: 74424

African (AFR) AF: 0.00169 AC: 70 AN: 41536

American (AMR) AF: 0.00418 AC: 64 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00685 AC: 33 AN: 4816

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 809 AN: 67994

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.0108 Hom.: 10

Bravo AF: 0.00592

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00932

EpiControl AF: 0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ETS1: BP4, BS1, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.8
DANN	Benign	0.80
PhyloP100		-0.33
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs118149282; hg19: chr11-128350288;