dbSNP rs860573: FEV:p.Gly119Gly (chr2-218982027-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017521.3(FEV):c.357C>T(p.Gly119Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 1,613,502 control chromosomes in the GnomAD database, including 3,708 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 0.082 ( 1164 hom., cov: 33)

Exomes 𝑓: 0.029 ( 2544 hom. )

Consequence

FEV
NM_017521.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

Publications

14 publications found

Variant links:

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]

FEV links:

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

LINC00608 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=1.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FEV	NM_017521.3 link	c.357C>T	p.Gly119Gly	synonymous_variant	Exon 3 of 3	ENST00000295727.2	NP_059991.1	Q99581
FEV	XM_047444822.1 link	c.72C>T	p.Gly24Gly	synonymous_variant	Exon 3 of 3		XP_047300778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FEV	ENST00000295727.2 link	c.357C>T	p.Gly119Gly	synonymous_variant	Exon 3 of 3	1	NM_017521.3	ENSP00000295727.1	Q99581
FEV	ENST00000470119.1 link	n.475C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
LINC00608	ENST00000627043.2 link	n.1201+2647G>A		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0815

AC:

12394

AN:

152140

Hom.:

1158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0273

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0645

GnomAD2 exomes

AF:

0.0555

AC:

13847

AN:

249650

AF XY:

0.0561

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0287

AC:

41938

AN:

1461246

Hom.:

2544

Cov.:

AF XY:

0.0313

AC XY:

22760

AN XY:

726954

show subpopulations

African (AFR)

AF:

0.236

AC:

7907

AN:

33462

American (AMR)

AF:

0.0239

AC:

1067

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

753

AN:

26114

East Asian (EAS)

AF:

0.116

AC:

4587

AN:

39686

South Asian (SAS)

AF:

0.144

AC:

12383

AN:

86250

European-Finnish (FIN)

AF:

0.0221

AC:

1174

AN:

53146

Middle Eastern (MID)

AF:

0.0633

AC:

362

AN:

5720

European-Non Finnish (NFE)

AF:

0.00969

AC:

10776

AN:

1111796

Other (OTH)

AF:

0.0485

AC:

2929

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

2316

4633

6949

9266

11582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0816

AC:

12431

AN:

152256

Hom.:

1164

Cov.:

AF XY:

0.0838

AC XY:

6243

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.218

AC:

9057

AN:

41538

American (AMR)

AF:

0.0388

AC:

594

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

105

AN:

3472

East Asian (EAS)

AF:

0.129

AC:

669

AN:

5180

South Asian (SAS)

AF:

0.158

AC:

766

AN:

4834

European-Finnish (FIN)

AF:

0.0273

AC:

290

AN:

10604

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0112

AC:

764

AN:

68008

Other (OTH)

AF:

0.0671

AC:

142

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

516

1032

1547

2063

2579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0361

Hom.:

521

Bravo

AF:

0.0870

Asia WGS

AF:

0.178

AC:

617

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over