rs2187642

chr12-11702690-A-Cchr12-11702690-A-T

Variant summary

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

The NM_001987.5(ETV6):c.34-49760A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,962 control chromosomes in the GnomAD database, including 22,124 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 0.50 (22124 hom., cov: 31)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV6	NM_001987.5	c.34-49760A>C		intron_variant		ENST00000396373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV6	ENST00000396373.9	c.34-49760A>C		intron_variant		1	NM_001987.5	P1
ETV6	ENST00000541426.1	n.218-49760A>C		intron_variant, non_coding_transcript_variant		4
ETV6	ENST00000544715.1	n.151-13897A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75325 AN: 151844 Hom.: 22120 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.496 AC: 75336 AN: 151962 Hom.: 22124 Cov.: 31 AF XY: 0.496 AC XY: 36856 AN XY: 74290

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.541

Alfa AF: 0.614 Hom.: 61987

Bravo AF: 0.485

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.46
Dann	Benign	0.44

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: rs2187642; hg19: chr12-11855624;