dbSNP rs4937333: ETS1:c.*1736A>G (chr11-128460625-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.491

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ETS1	NM_001143820.2 link	c.*1736A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000392668.8	NP_001137292.1	P14921-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ETS1	ENST00000392668 link	c.*1736A>G	3_prime_UTR_variant	Exon 10 of 10	1	NM_001143820.2	ENSP00000376436.3	P14921-3
ETS1	ENST00000319397 link	c.*1736A>G	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000324578.5	P14921-1
ETS1	ENST00000535549 link	c.*1736A>G	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000441430.1	P14921-4
ETS1	ENST00000526145 link	c.*1736A>G	3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000433500.1	P14921-2

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69672

AN:

151898

Hom.:

17011

Cov.:

show subpopulations

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:

AN:

142

Hom.:

Cov.:

AF XY:

0.487

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.462

AC XY:

34356

AN XY:

74304

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31275358) -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over