rs750182232

Variant names:

• chr11-128480443-C-G
• rs750182232
• NM_001143820.2:c.871G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-128480443-C-G
• chr11-128480443-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001143820.2(ETS1):​c.871G>C​(p.Gly291Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,484 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ETS1 NM_001143820.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.84
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	NM_001143820.2	MANE Select	c.871G>C	p.Gly291Arg	missense	Exon 8 of 10	NP_001137292.1	P14921-3
	ETS1	NM_005238.4		c.739G>C	p.Gly247Arg	missense	Exon 6 of 8	NP_005229.1	P14921-1
	ETS1	NM_001162422.2		c.91G>C	p.Gly31Arg	missense	Exon 2 of 4	NP_001155894.1	P14921-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	ENST00000392668.8	TSL:1 MANE Select	c.871G>C	p.Gly291Arg	missense	Exon 8 of 10	ENSP00000376436.3	P14921-3
	ETS1	ENST00000319397.7	TSL:1	c.739G>C	p.Gly247Arg	missense	Exon 6 of 8	ENSP00000324578.5	P14921-1
	ETS1	ENST00000531611.5	TSL:1	c.739G>C	p.Gly247Arg	missense	Exon 6 of 7	ENSP00000435666.1	P14921-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459484 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725622

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109986

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.30	N
REVEL	Uncertain	0.31
Sift	Benign	0.79	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.92
MutPred		0.31		Gain of solvent accessibility (P = 0.019)
MVP		0.82
MPC		1.3
ClinPred		0.76	D
GERP RS		5.6
Varity_R		0.20
gMVP		0.58
Mutation Taster		=22/78	disease causing

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: rs750182232; hg19: chr11-128350338;