12-11650344-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001987.5(ETV6):c.33+191dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (32531 hom., cov: 0)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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 -10 ACMG points.

• BP6: Variant 12-11650344-T-TC is Benign according to our data. Variant chr12-11650344-T-TC is described in ClinVar as [Benign]. Clinvar id is 1276049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV6	NM_001987.5	c.33+191dup		intron_variant		ENST00000396373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV6	ENST00000396373.9	c.33+191dup		intron_variant		1	NM_001987.5	P1
ETV6	ENST00000541426.1	n.217+191dup		intron_variant, non_coding_transcript_variant		4
ETV6	ENST00000544715.1	n.150+191dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.677 AC: 85992 AN: 127040 Hom.: 32516 Cov.: 0

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.743

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.677 AC: 86032 AN: 127150 Hom.: 32531 Cov.: 0 AF XY: 0.675 AC XY: 40619 AN XY: 60204

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.692

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs145552837; hg19: chr12-11803278;