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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.0555

AC:

13847

AN:

249650

Hom.:

1056

AF XY:

0.0561

AC XY:

7589

AN XY:

135366

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 SAS exome

AF:

0.148

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

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0288

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.00969

Gnomad4 OTH exome

AF:

0.0485

GnomAD4 genome

AF:

0.0816

AC:

12431

AN:

152256

Hom.:

1164

Cov.:

AF XY:

0.0838

AC XY:

6243

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.0388

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.129

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.0273

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0671

Alfa

AF:

0.0303

Hom.:

339

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

DANN

Benign

0.97

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over