rs17167666

Variant names:

• chr7-13931798-T-C
• rs17167666
• NM_004956.5:c.555-49A>G

Variant summary

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

The NM_004956.5(ETV1):​c.555-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,598,490 control chromosomes in the GnomAD database, including 364 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 0.029 (190 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (174 hom.)
• Consequence: ETV1 NM_004956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

ETV1 (HGNC:3490): (ETS variant transcription factor 1) This gene encodes a member of the ETS (E twenty-six) family of transcription factors. The ETS proteins regulate many target genes that modulate biological processes like cell growth, angiogenesis, migration, proliferation and differentiation. All ETS proteins contain an ETS DNA-binding domain that binds to DNA sequences containing the consensus 5'-CGGA[AT]-3'. The protein encoded by this gene contains a conserved short acidic transactivation domain (TAD) in the N-terminal region, in addition to the ETS DNA-binding domain in the C-terminal region. This gene is involved in chromosomal translocations, which result in multiple fusion proteins including EWS-ETV1 in Ewing sarcoma and at least 10 ETV1 partners (see PMID: 19657377, Table 1) in prostate cancer. In addition to chromosomal rearrangement, this gene is overexpressed in prostate cancer, melanoma and gastrointestinal stromal tumor. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV1	NM_004956.5	c.555-49A>G		intron_variant	Intron 8 of 13	ENST00000430479.6	NP_004947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV1	ENST00000430479.6	c.555-49A>G		intron_variant	Intron 8 of 13	1	NM_004956.5	ENSP00000405327.1
ETV1	ENST00000405358.8	c.597-49A>G		intron_variant	Intron 6 of 11	5		ENSP00000384085.4
ETV1	ENST00000405218.6	c.555-49A>G		intron_variant	Intron 7 of 12	5		ENSP00000385551.2
ETV1	ENST00000403685.5	c.501-49A>G		intron_variant	Intron 6 of 11	1		ENSP00000385686.1
ETV1	ENST00000403527.6	c.435-49A>G		intron_variant	Intron 4 of 9	1		ENSP00000384138.1
ETV1	ENST00000438956.6	c.381-49A>G		intron_variant	Intron 3 of 8	1		ENSP00000393078.2
ETV1	ENST00000443137.5	n.555-49A>G		intron_variant	Intron 8 of 14	2		ENSP00000413836.1

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4421 AN: 152164 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00948 AC: 2296 AN: 242316 Hom.: 87 AF XY: 0.00782 AC XY: 1029 AN XY: 131542

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00647

Gnomad ASJ exome AF: 0.00711

Gnomad EAS exome AF: 0.0000559

Gnomad SAS exome AF: 0.00338

Gnomad FIN exome AF: 0.000282

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00520 AC: 7516 AN: 1446208 Hom.: 174 Cov.: 30 AF XY: 0.00492 AC XY: 3529 AN XY: 716874

Gnomad4 AFR exome AF: 0.0957

Gnomad4 AMR exome AF: 0.00703

Gnomad4 ASJ exome AF: 0.00807

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.00287

Gnomad4 FIN exome AF: 0.000489

Gnomad4 NFE exome AF: 0.00268

Gnomad4 OTH exome AF: 0.00947

GnomAD4 genome AF: 0.0291 AC: 4430 AN: 152282 Hom.: 190 Cov.: 33 AF XY: 0.0279 AC XY: 2074 AN XY: 74468

Gnomad4 AFR AF: 0.0963

Gnomad4 AMR AF: 0.00995

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0145 Hom.: 10

Bravo AF: 0.0330

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.4
DANN	Benign	0.56

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: rs17167666; hg19: chr7-13971423;