12-11754194-C-T

Position:

• chr12-11754194-C-T

Variant summary

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

The ENST00000396373.9(ETV6):​c.163+1615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,210 control chromosomes in the GnomAD database, including 1,187 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 0.10 (1187 hom., cov: 32)
• Consequence: ETV6 ENST00000396373.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV6	NM_001987.5	c.163+1615C>T		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+1615C>T		intron_variant		1	NM_001987.5	ENSP00000379658	P1
ETV6	ENST00000545027.1	c.79+1615C>T		intron_variant		5		ENSP00000441463
ETV6	ENST00000541426.1	n.347+1615C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15872 AN: 152092 Hom.: 1185 Cov.: 32

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.104 AC: 15871 AN: 152210 Hom.: 1187 Cov.: 32 AF XY: 0.112 AC XY: 8368 AN XY: 74394

Gnomad4 AFR AF: 0.0298

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.108

Alfa AF: 0.112 Hom.: 1363

Bravo AF: 0.0875

Asia WGS AF: 0.247 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.027
DANN	Benign	0.55

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: rs2051526; hg19: chr12-11907128; COSMIC: COSV67148369; COSMIC: COSV67148369;