rs1573613

Variant names:

• chr12-11894684-T-C
• rs1573613
• NM_001987.5:c.*3638T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.364
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• thrombocytopenia 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• acute myeloid leukemia

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp
• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001987.5. 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
	ETV6	NM_001987.5	MANE Select	c.*3638T>C		3_prime_UTR	Exon 8 of 8	NP_001978.1	P41212
	ETV6	NM_001413913.1		c.*3638T>C		3_prime_UTR	Exon 8 of 8	NP_001400842.1
	ETV6	NM_001413914.1		c.*3638T>C		3_prime_UTR	Exon 9 of 9	NP_001400843.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV6	ENST00000396373.9	TSL:1 MANE Select	c.*3638T>C		3_prime_UTR	Exon 8 of 8	ENSP00000379658.3	P41212
	ETV6	ENST00000937343.1		c.*3638T>C		3_prime_UTR	Exon 7 of 7	ENSP00000607402.1

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

African (AFR) AF: 0.577 AC: 2237 AN: 3880

American (AMR) AF: 0.590 AC: 1475 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 2365 AN: 5114

East Asian (EAS) AF: 0.491 AC: 5585 AN: 11384

South Asian (SAS) AF: 0.426 AC: 299 AN: 702

European-Finnish (FIN) AF: 0.379 AC: 22 AN: 58

Middle Eastern (MID) AF: 0.474 AC: 234 AN: 494

European-Non Finnish (NFE) AF: 0.440 AC: 21980 AN: 49940

Other (OTH) AF: 0.474 AC: 3205 AN: 6762

GnomAD4 genome AF: 0.482 AC: 73317 AN: 151996 Hom.: 18214 Cov.: 32 AF XY: 0.481 AC XY: 35760 AN XY: 74280

African (AFR) AF: 0.573 AC: 23721 AN: 41428

American (AMR) AF: 0.569 AC: 8688 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1601 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2340 AN: 5160

South Asian (SAS) AF: 0.415 AC: 2004 AN: 4824

European-Finnish (FIN) AF: 0.405 AC: 4278 AN: 10566

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29075 AN: 67956

Other (OTH) AF: 0.488 AC: 1031 AN: 2112

Alfa AF: 0.458 Hom.: 20543

Bravo AF: 0.503

Asia WGS AF: 0.430 AC: 1496 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	-0.67
CADD	Benign	4.3
DANN	Benign	0.62
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1573613;

hg19: chr12-12047618;