NM_017521.3:c.128-191dupA

Variant names:

• chr2-218982446-C-CT
• rs35898226
• NM_017521.3:c.128-191dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_017521.3(FEV):​c.128-191dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 152,318 control chromosomes in the GnomAD database, including 587 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (587 hom., cov: 32)
• Consequence: FEV NM_017521.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.90
• Publications: 0 publications found

Genes affected

FEV (HGNC:18562): (FEV transcription factor, ETS family member) This gene belongs to the ETS transcription factor family. ETS family members have a highly conserved 85-amino acid ETS domain that binds purine-rich DNA sequences. The alanine-rich C-terminus of this gene indicates that it may act as a transcription repressor. This gene is exclusively expressed in neurons of the central serotonin (5-HT) system, a system implicated in the pathogeny of such psychiatric diseases as depression, anxiety, and eating disorders. In some types of Ewing tumors, this gene is fused to the Ewing sarcoma (EWS) gene following chromosome translocations. [provided by RefSeq, Jul 2008]

LINC00608 (HGNC:27179): (long intergenic non-protein coding RNA 608)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-218982446-C-CT is Benign according to our data. Variant chr2-218982446-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1258531.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017521.3. 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
	FEV	NM_017521.3	MANE Select	c.128-191dupA		intron	N/A	NP_059991.1	Q99581

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FEV	ENST00000295727.2	TSL:1 MANE Select	c.128-191_128-190insA		intron	N/A	ENSP00000295727.1	Q99581
	FEV	ENST00000470119.1	TSL:2	n.246-191_246-190insA		intron	N/A
	LINC00608	ENST00000627043.2	TSL:5	n.1201+3066_1201+3067insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7192 AN: 152200 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0382

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

GnomAD4 genome AF: 0.0475 AC: 7232 AN: 152318 Hom.: 587 Cov.: 32 AF XY: 0.0468 AC XY: 3490 AN XY: 74502

African (AFR) AF: 0.163 AC: 6759 AN: 41532

American (AMR) AF: 0.0177 AC: 271 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5186

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68038

Other (OTH) AF: 0.0378 AC: 80 AN: 2116

Alfa AF: 0.0398 Hom.: 26

Bravo AF: 0.0531

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.9
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: rs35898226; hg19: chr2-219847168;