chr12-11702690-A-C

Variant names:

• chr12-11702690-A-C
• rs2187642
• NM_001987.5:c.34-49760A>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.34-49760A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,962 control chromosomes in the GnomAD database, including 22,124 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 0.50 (22124 hom., cov: 31)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5	c.34-49760A>C		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.34-49760A>C		intron_variant	Intron 1 of 7	1	NM_001987.5	ENSP00000379658.3
ETV6	ENST00000541426.1	n.218-49760A>C		intron_variant	Intron 1 of 3	4
ETV6	ENST00000544715.1	n.151-13897A>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75325 AN: 151844 Hom.: 22120 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.496 AC: 75336 AN: 151962 Hom.: 22124 Cov.: 31 AF XY: 0.496 AC XY: 36856 AN XY: 74290

African (AFR) AF: 0.160 AC: 6653 AN: 41462

American (AMR) AF: 0.648 AC: 9881 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2364 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2461 AN: 5170

South Asian (SAS) AF: 0.520 AC: 2498 AN: 4806

European-Finnish (FIN) AF: 0.628 AC: 6632 AN: 10560

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43018 AN: 67940

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

Alfa AF: 0.590 Hom.: 87581

Bravo AF: 0.485

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.44
PhyloP100		-0.58
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: rs2187642; hg19: chr12-11855624;