12-11852786-C-T

Variant names:

• chr12-11852786-C-T
• rs1894307
• NM_001987.5:c.329-641C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001987.5(ETV6):​c.329-641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,158 control chromosomes in the GnomAD database, including 1,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1789 hom., cov: 33)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• acute myeloid leukemia

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5	c.329-641C>T		intron_variant	Intron 3 of 7	ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.329-641C>T		intron_variant	Intron 3 of 7	1	NM_001987.5	ENSP00000379658.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21668 AN: 152040 Hom.: 1788 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.143 AC: 21690 AN: 152158 Hom.: 1789 Cov.: 33 AF XY: 0.145 AC XY: 10796 AN XY: 74368

African (AFR) AF: 0.117 AC: 4865 AN: 41514

American (AMR) AF: 0.145 AC: 2220 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2096 AN: 5168

South Asian (SAS) AF: 0.0876 AC: 422 AN: 4820

European-Finnish (FIN) AF: 0.197 AC: 2079 AN: 10576

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9175 AN: 68004

Other (OTH) AF: 0.133 AC: 280 AN: 2110

Alfa AF: 0.133 Hom.: 2465

Bravo AF: 0.143

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.65
DANN	Benign	0.67
PhyloP100		-0.96
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

Other links and lift over

dbSNP: rs1894307; hg19: chr12-12005720;