12-11650349-C-CG

Variant summary

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

The NM_001987.5(ETV6):c.33+189_33+190insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 149,316 control chromosomes in the GnomAD database, including 630 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.044 (630 hom., cov: 24)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 12-11650349-C-CG is Benign according to our data. Variant chr12-11650349-C-CG is described in ClinVar as [Benign]. Clinvar id is 1229805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV6	NM_001987.5	c.33+189_33+190insG		intron_variant		ENST00000396373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV6	ENST00000396373.9	c.33+189_33+190insG		intron_variant		1	NM_001987.5	P1
ETV6	ENST00000541426.1	n.217+189_217+190insG		intron_variant, non_coding_transcript_variant		4
ETV6	ENST00000544715.1	n.150+189_150+190insG		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6618 AN: 149204 Hom.: 626 Cov.: 24

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000646

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000371

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0445 AC: 6638 AN: 149316 Hom.: 630 Cov.: 24 AF XY: 0.0433 AC XY: 3158 AN XY: 72868

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000431

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000371

Gnomad4 OTH AF: 0.0293

Bravo AF: 0.0503

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

Mar 24, 2019

- -

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: rs145572199; hg19: chr12-11803283;