NM_001987.5:c.163+25376G>T

Variant names:

• chr12-11777955-G-T
• rs1894331
• NM_001987.5:c.163+25376G>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.163+25376G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,990 control chromosomes in the GnomAD database, including 21,595 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 0.49 (21595 hom., cov: 31)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.688 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.163+25376G>T		intron	N/A	NP_001978.1
	ETV6	NM_001413913.1		c.160+25376G>T		intron	N/A	NP_001400842.1
	ETV6	NM_001413914.1		c.136+25376G>T		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.163+25376G>T		intron	N/A	ENSP00000379658.3
	ETV6	ENST00000545027.1	TSL:5	c.79+25376G>T		intron	N/A	ENSP00000441463.1
	ETV6	ENST00000541426.1	TSL:4	n.347+25376G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75132 AN: 151872 Hom.: 21582 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.494 AC: 75159 AN: 151990 Hom.: 21595 Cov.: 31 AF XY: 0.494 AC XY: 36677 AN XY: 74272

African (AFR) AF: 0.185 AC: 7676 AN: 41490

American (AMR) AF: 0.699 AC: 10664 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2603 AN: 5182

South Asian (SAS) AF: 0.466 AC: 2245 AN: 4822

European-Finnish (FIN) AF: 0.561 AC: 5914 AN: 10534

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41794 AN: 67924

Other (OTH) AF: 0.545 AC: 1146 AN: 2104

Alfa AF: 0.558 Hom.: 4225

Bravo AF: 0.495

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		0.032
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: rs1894331; hg19: chr12-11930889;