12-11650453-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001987.5(ETV6):c.33+293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (56 hom., cov: 17)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-11650453-C-T is Benign according to our data. Variant chr12-11650453-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1209048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV6	NM_001987.5	c.33+293C>T		intron_variant		ENST00000396373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV6	ENST00000396373.9	c.33+293C>T		intron_variant		1	NM_001987.5	P1
ETV6	ENST00000541426.1	n.217+293C>T		intron_variant, non_coding_transcript_variant		4
ETV6	ENST00000544715.1	n.150+293C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 2786 AN: 107662 Hom.: 56 Cov.: 17

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.00911

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0341

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.00934

Gnomad MID AF: 0.0862

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0465

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

GnomAD4 genome AF: 0.0259 AC: 2789 AN: 107724 Hom.: 56 Cov.: 17 AF XY: 0.0268 AC XY: 1311 AN XY: 48868

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.0341

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0504

Gnomad4 FIN AF: 0.00934

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0476

Alfa AF: 0.0210 Hom.: 10

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	10
Dann	Benign	0.84

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: rs78053111; hg19: chr12-11803387;