chr7-13931798-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0938 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.555-49A>G		intron	N/A	NP_004947.2
	ETV1	NM_001370555.1		c.555-49A>G		intron	N/A	NP_001357484.1
	ETV1	NM_001370556.1		c.507-49A>G		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.555-49A>G		intron	N/A	ENSP00000405327.1
	ETV1	ENST00000405358.8	TSL:5	c.597-49A>G		intron	N/A	ENSP00000384085.4
	ETV1	ENST00000405218.6	TSL:5	c.555-49A>G		intron	N/A	ENSP00000385551.2

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

GnomAD2 exomes AF: 0.00948 AC: 2296 AN: 242316 AF XY: 0.00782

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 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

African (AFR) AF: 0.0957 AC: 3164 AN: 33078

American (AMR) AF: 0.00703 AC: 309 AN: 43982

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 206 AN: 25520

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39376

South Asian (SAS) AF: 0.00287 AC: 244 AN: 84886

European-Finnish (FIN) AF: 0.000489 AC: 26 AN: 53180

Middle Eastern (MID) AF: 0.00791 AC: 45 AN: 5690

European-Non Finnish (NFE) AF: 0.00268 AC: 2955 AN: 1100804

Other (OTH) AF: 0.00947 AC: 565 AN: 59692

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

African (AFR) AF: 0.0963 AC: 4000 AN: 41542

American (AMR) AF: 0.00995 AC: 152 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00285 AC: 194 AN: 68038

Other (OTH) AF: 0.0170 AC: 36 AN: 2112

Alfa AF: 0.0139 Hom.: 25

Bravo AF: 0.0330

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.4
DANN	Benign	0.56
PhyloP100		1.1
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: rs17167666; hg19: chr7-13971423;