rs1573612

chr12-11894495-T-C

Variant summary

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

The NM_001987.5(ETV6):c.*3449T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 232,804 control chromosomes in the GnomAD database, including 27,507 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 0.49 (18595 hom., cov: 31)
  • Exomes 𝑓: 0.47 (8912 hom.)
• Consequence: ETV6 NM_001987.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV6	NM_001987.5	c.*3449T>C		3_prime_UTR_variant	8/8	ENST00000396373.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV6	ENST00000396373.9	c.*3449T>C		3_prime_UTR_variant	8/8	1	NM_001987.5	P1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74076 AN: 151868 Hom.: 18561 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.468 AC: 37815 AN: 80818 Hom.: 8912 Cov.: 0 AF XY: 0.465 AC XY: 17286 AN XY: 37152

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.473

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.488 AC: 74168 AN: 151986 Hom.: 18595 Cov.: 31 AF XY: 0.488 AC XY: 36224 AN XY: 74274

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.493

Alfa AF: 0.458 Hom.: 13618

Bravo AF: 0.507

Asia WGS AF: 0.432 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.14
Dann	Benign	0.34

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: rs1573612; hg19: chr12-12047429;