NM_004956.5:c.803-8474C>T

Variant names:

• chr7-13919781-G-A
• rs3801094
• NM_004956.5:c.803-8474C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004956.5(ETV1):​c.803-8474C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,452 control chromosomes in the GnomAD database, including 9,421 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 0.35 (9421 hom., cov: 31)
• Consequence: ETV1 NM_004956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV1	NM_004956.5	MANE Select	c.803-8474C>T		intron	N/A	NP_004947.2
	ETV1	NM_001370555.1		c.803-8474C>T		intron	N/A	NP_001357484.1
	ETV1	NM_001370556.1		c.755-8474C>T		intron	N/A	NP_001357485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV1	ENST00000430479.6	TSL:1 MANE Select	c.803-8474C>T		intron	N/A	ENSP00000405327.1
	ETV1	ENST00000405358.8	TSL:5	c.845-8474C>T		intron	N/A	ENSP00000384085.4
	ETV1	ENST00000405218.6	TSL:5	c.803-8474C>T		intron	N/A	ENSP00000385551.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52315 AN: 151334 Hom.: 9422 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.345 AC: 52324 AN: 151452 Hom.: 9421 Cov.: 31 AF XY: 0.345 AC XY: 25531 AN XY: 73946

African (AFR) AF: 0.268 AC: 11057 AN: 41280

American (AMR) AF: 0.339 AC: 5166 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 943 AN: 3462

East Asian (EAS) AF: 0.258 AC: 1326 AN: 5148

South Asian (SAS) AF: 0.371 AC: 1780 AN: 4804

European-Finnish (FIN) AF: 0.389 AC: 4044 AN: 10394

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26900 AN: 67838

Other (OTH) AF: 0.320 AC: 672 AN: 2100

Alfa AF: 0.381 Hom.: 4959

Bravo AF: 0.335

Asia WGS AF: 0.303 AC: 1049 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.34
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3801094; hg19: chr7-13959406;