rs916041

Variant names:

• chr12-11659396-A-G
• rs916041
• NM_001987.5:c.33+9236A>G

Variant summary

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

The NM_001987.5(ETV6):​c.33+9236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,016 control chromosomes in the GnomAD database, including 13,006 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 0.37 (13006 hom., cov: 31)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5	c.33+9236A>G		intron_variant	Intron 1 of 7	ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.33+9236A>G		intron_variant	Intron 1 of 7	1	NM_001987.5	ENSP00000379658.3
ETV6	ENST00000541426.1	n.217+9236A>G		intron_variant	Intron 1 of 3	4
ETV6	ENST00000544715.1	n.150+9236A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56866 AN: 151898 Hom.: 13002 Cov.: 31

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.374 AC: 56873 AN: 152016 Hom.: 13006 Cov.: 31 AF XY: 0.375 AC XY: 27867 AN XY: 74288

African (AFR) AF: 0.106 AC: 4384 AN: 41502

American (AMR) AF: 0.465 AC: 7104 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1639 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1382 AN: 5164

South Asian (SAS) AF: 0.389 AC: 1876 AN: 4820

European-Finnish (FIN) AF: 0.474 AC: 4995 AN: 10542

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34086 AN: 67922

Other (OTH) AF: 0.402 AC: 851 AN: 2116

Alfa AF: 0.458 Hom.: 46217

Bravo AF: 0.360

Asia WGS AF: 0.327 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs916041; hg19: chr12-11812330;