chr11-128460625-T-C

Position:

• chr11-128460625-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2	c.*1736A>G		3_prime_UTR_variant	10/10	ENST00000392668.8	NP_001137292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS1	ENST00000392668.8	c.*1736A>G		3_prime_UTR_variant	10/10	1	NM_001143820.2	ENSP00000376436
ETS1	ENST00000319397.7	c.*1736A>G		3_prime_UTR_variant	8/8	1		ENSP00000324578	P1
ETS1	ENST00000535549.5	c.*1736A>G		3_prime_UTR_variant	4/4	1		ENSP00000441430
ETS1	ENST00000526145.6	c.*1736A>G		3_prime_UTR_variant	7/7	5		ENSP00000433500

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

Gnomad4 EAS exome AF: 0.507

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.490

Alfa AF: 0.507 Hom.: 26538

Bravo AF: 0.440

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2019	This variant is associated with the following publications: (PMID: 31275358) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.6
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4937333; hg19: chr11-128330520;