NM_001987.5:c.164-16542T>C

Variant names:

• chr12-11822598-T-C
• rs2710287
• NM_001987.5:c.164-16542T>C

Variant summary

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

The NM_001987.5(ETV6):​c.164-16542T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,180 control chromosomes in the GnomAD database, including 42,382 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 0.74 (42382 hom., cov: 32)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758
• Publications: 8 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=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV6	NM_001987.5	MANE Select	c.164-16542T>C		intron	N/A	NP_001978.1
	ETV6	NM_001413913.1		c.161-16542T>C		intron	N/A	NP_001400842.1
	ETV6	NM_001413914.1		c.137-16542T>C		intron	N/A	NP_001400843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV6	ENST00000396373.9	TSL:1 MANE Select	c.164-16542T>C		intron	N/A	ENSP00000379658.3
	ETV6	ENST00000545027.1	TSL:5	c.80-16542T>C		intron	N/A	ENSP00000441463.1
	ETV6	ENST00000541426.1	TSL:4	n.348-3046T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111866 AN: 152062 Hom.: 42329 Cov.: 32

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.736 AC: 111976 AN: 152180 Hom.: 42382 Cov.: 32 AF XY: 0.735 AC XY: 54687 AN XY: 74394

African (AFR) AF: 0.923 AC: 38339 AN: 41534

American (AMR) AF: 0.624 AC: 9537 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3810 AN: 5176

South Asian (SAS) AF: 0.683 AC: 3291 AN: 4820

European-Finnish (FIN) AF: 0.752 AC: 7959 AN: 10582

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44347 AN: 67998

Other (OTH) AF: 0.721 AC: 1524 AN: 2114

Alfa AF: 0.671 Hom.: 32698

Bravo AF: 0.739

Asia WGS AF: 0.709 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.64
PhyloP100		0.76
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: rs2710287; hg19: chr12-11975532;