rs2237291

Variant names:

• chr7-13932682-C-T
• rs2237291
• NM_004956.5:c.555-933G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004956.5(ETV1):​c.555-933G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,890 control chromosomes in the GnomAD database, including 8,823 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 0.33 (8823 hom., cov: 32)
• Consequence: ETV1 NM_004956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV1	NM_004956.5	MANE Select	c.555-933G>A		intron	N/A	NP_004947.2
	ETV1	NM_001370555.1		c.555-933G>A		intron	N/A	NP_001357484.1
	ETV1	NM_001370556.1		c.507-933G>A		intron	N/A	NP_001357485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV1	ENST00000430479.6	TSL:1 MANE Select	c.555-933G>A		intron	N/A	ENSP00000405327.1
	ETV1	ENST00000405358.8	TSL:5	c.597-933G>A		intron	N/A	ENSP00000384085.4
	ETV1	ENST00000405218.6	TSL:5	c.555-933G>A		intron	N/A	ENSP00000385551.2

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50856 AN: 151770 Hom.: 8831 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.335 AC: 50852 AN: 151890 Hom.: 8823 Cov.: 32 AF XY: 0.337 AC XY: 25036 AN XY: 74236

African (AFR) AF: 0.246 AC: 10180 AN: 41420

American (AMR) AF: 0.389 AC: 5934 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1434 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2542 AN: 5148

South Asian (SAS) AF: 0.395 AC: 1898 AN: 4808

European-Finnish (FIN) AF: 0.352 AC: 3703 AN: 10524

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23868 AN: 67956

Other (OTH) AF: 0.351 AC: 740 AN: 2110

Alfa AF: 0.349 Hom.: 21939

Bravo AF: 0.335

Asia WGS AF: 0.415 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.74
PhyloP100		1.1
Mutation Taster		=99/1	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: rs2237291; hg19: chr7-13972307; COSMIC: COSV54136092;