rs1573613

Positions:

• chr12-11894684-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
ETV6	NM_001987.5	c.*3638T>C		3_prime_UTR_variant	8/8	ENST00000396373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV6	ENST00000396373.9	c.*3638T>C		3_prime_UTR_variant	8/8	1	NM_001987.5	P1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73229 AN: 151876 Hom.: 18186 Cov.: 32

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.: 0 AF XY: 0.460 AC XY: 17082 AN XY: 37152

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.: 32 AF XY: 0.481 AC XY: 35760 AN XY: 74280

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2020

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

Other links and lift over

dbSNP: rs1573613; hg19: chr12-12047618;