12-11786594-G-A

Position:

• chr12-11786594-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001987.5(ETV6):​c.163+34015G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,192 control chromosomes in the GnomAD database, including 1,878 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 0.13 (1878 hom., cov: 32)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV6	NM_001987.5	c.163+34015G>A		intron_variant		ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.163+34015G>A		intron_variant		1	NM_001987.5	ENSP00000379658	P1
ETV6	ENST00000545027.1	c.79+34015G>A		intron_variant		5		ENSP00000441463
ETV6	ENST00000541426.1	n.347+34015G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19994 AN: 152074 Hom.: 1879 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.131 AC: 20001 AN: 152192 Hom.: 1878 Cov.: 32 AF XY: 0.140 AC XY: 10382 AN XY: 74408

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.141

Alfa AF: 0.153 Hom.: 1060

Bravo AF: 0.115

Asia WGS AF: 0.311 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs10491990; hg19: chr12-11939528; COSMIC: COSV67148416;