11-128460625-T-C

Variant names:

• chr11-128460625-T-C
• rs4937333
• NM_001143820.2:c.*1736A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001143820.2(ETS1):​c.*1736A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,158 control chromosomes in the GnomAD database, including 17,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17011 hom., cov: 31)
  • Exomes 𝑓: 0.51 (17 hom.)
• Consequence: ETS1 NM_001143820.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.491
• Publications: 32 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 11-128460625-T-C is Benign according to our data. Variant chr11-128460625-T-C is described in ClinVar as Benign. ClinVar VariationId is 1276850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	NM_001143820.2	MANE Select	c.*1736A>G		3_prime_UTR	Exon 10 of 10	NP_001137292.1	P14921-3
	ETS1	NM_005238.4		c.*1736A>G		3_prime_UTR	Exon 8 of 8	NP_005229.1	P14921-1
	ETS1	NM_001330451.2		c.*1736A>G		3_prime_UTR	Exon 7 of 7	NP_001317380.1	P14921-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS1	ENST00000392668.8	TSL:1 MANE Select	c.*1736A>G		3_prime_UTR	Exon 10 of 10	ENSP00000376436.3	P14921-3
	ETS1	ENST00000319397.7	TSL:1	c.*1736A>G		3_prime_UTR	Exon 8 of 8	ENSP00000324578.5	P14921-1
	ETS1	ENST00000535549.5	TSL:1	c.*1736A>G		3_prime_UTR	Exon 4 of 4	ENSP00000441430.1	P14921-4

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69672 AN: 151898 Hom.: 17011 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.514 AC: 73 AN: 142 Hom.: 17 Cov.: 0 AF XY: 0.487 AC XY: 38 AN XY: 78

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.507 AC: 69 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.458 AC: 69678 AN: 152016 Hom.: 17011 Cov.: 31 AF XY: 0.462 AC XY: 34356 AN XY: 74304

African (AFR) AF: 0.289 AC: 11972 AN: 41468

American (AMR) AF: 0.426 AC: 6521 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2015 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2914 AN: 5162

South Asian (SAS) AF: 0.552 AC: 2663 AN: 4826

European-Finnish (FIN) AF: 0.590 AC: 6206 AN: 10520

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35703 AN: 67962

Other (OTH) AF: 0.490 AC: 1036 AN: 2114

Alfa AF: 0.500 Hom.: 32688

Bravo AF: 0.440

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.6
DANN	Benign	0.88
PhyloP100		0.49
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: rs4937333; hg19: chr11-128330520; COSMIC: COSV107401136; COSMIC: COSV107401136;