Genetic Variant ETV6:c.*3638T>C (chr12-11894684-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_001987.5(ETV6):c.*3638T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 232,830 control chromosomes in the GnomAD database, including 26,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18214 hom., cov: 32)

Exomes 𝑓: 0.46 ( 8730 hom. )

Consequence

ETV6
NM_001987.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.364

Variant links:

Genes affected

ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

ETV6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-11894684-T-C is Benign according to our data. Variant chr12-11894684-T-C is described in ClinVar as [Benign]. Clinvar id is 1183803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5 link	c.*3638T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000396373.9	NP_001978.1	P41212A0A0S2Z3C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9 link	c.*3638T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001987.5	ENSP00000379658.3		P41212

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73229

AN:

151876

Hom.:

18186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.489

GnomAD4 exome

AF:

0.463

AC:

37402

AN:

80834

Hom.:

8730

Cov.:

AF XY:

0.460

AC XY:

17082

AN XY:

37152

show subpopulations

Gnomad4 AFR exome

AF:

0.577

Gnomad4 AMR exome

AF:

0.590

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.440

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.482

AC:

73317

AN:

151996

Hom.:

18214

Cov.:

AF XY:

0.481

AC XY:

35760

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.428

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.450

Hom.:

15161

Bravo

AF:

0.503

Asia WGS

AF:

0.430

AC:

1496

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

- -

Jul 14, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24886876) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.3

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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