rs2724635

Positions:

• chr12-11747039-G-A
• chr12-11747039-G-C

Variant summary

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

The NM_001987.5(ETV6):​c.34-5411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,824 control chromosomes in the GnomAD database, including 24,381 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 0.56 (24381 hom., cov: 30)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV6	NM_001987.5	c.34-5411G>A		intron_variant		ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.34-5411G>A		intron_variant		1	NM_001987.5	ENSP00000379658	P1
ETV6	ENST00000541426.1	n.218-5411G>A		intron_variant, non_coding_transcript_variant		4
ETV6	ENST00000544715.1	n.308-5411G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84296 AN: 151706 Hom.: 24369 Cov.: 30

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.556 AC: 84339 AN: 151824 Hom.: 24381 Cov.: 30 AF XY: 0.555 AC XY: 41163 AN XY: 74184

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.581

Alfa AF: 0.598 Hom.: 13838

Bravo AF: 0.552

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.72

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: rs2724635; hg19: chr12-11899973;