chr12-11747039-G-A

Variant names:

• chr12-11747039-G-A
• rs2724635
• NM_001987.5:c.34-5411G>A

Variant summary

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

The NM_001987.5(ETV6):​c.34-5411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,824 control chromosomes in the GnomAD database, including 24,381 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 0.56 (24381 hom., cov: 30)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 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.34-5411G>A		intron	N/A	NP_001978.1
	ETV6	NM_001413913.1		c.34-5414G>A		intron	N/A	NP_001400842.1
	ETV6	NM_001413914.1		c.6+3097G>A		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.34-5411G>A		intron	N/A	ENSP00000379658.3
	ETV6	ENST00000541426.1	TSL:4	n.218-5411G>A		intron	N/A
	ETV6	ENST00000544715.1	TSL:3	n.308-5411G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84296 AN: 151706 Hom.: 24369 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.556 AC: 84339 AN: 151824 Hom.: 24381 Cov.: 30 AF XY: 0.555 AC XY: 41163 AN XY: 74184

African (AFR) AF: 0.396 AC: 16373 AN: 41384

American (AMR) AF: 0.661 AC: 10082 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2462 AN: 5154

South Asian (SAS) AF: 0.494 AC: 2370 AN: 4802

European-Finnish (FIN) AF: 0.628 AC: 6615 AN: 10526

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42183 AN: 67922

Other (OTH) AF: 0.581 AC: 1225 AN: 2108

Alfa AF: 0.599 Hom.: 15444

Bravo AF: 0.552

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		0.62
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: rs2724635; hg19: chr12-11899973;