rs860573

Positions:

• chr2-218982027-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017521.3(FEV):​c.357C>T​(p.Gly119=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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

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/exons	MANE	UniProt
FEV	NM_017521.3	c.357C>T	p.Gly119=	synonymous_variant	3/3	ENST00000295727.2
FEV	XM_047444822.1	c.72C>T	p.Gly24=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FEV	ENST00000295727.2	c.357C>T	p.Gly119=	synonymous_variant	3/3	1	NM_017521.3	P1
LINC00608	ENST00000627043.2	n.1201+2647G>A		intron_variant, non_coding_transcript_variant		5
FEV	ENST00000470119.1	n.475C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0815 AC: 12394 AN: 152140 Hom.: 1158 Cov.: 33

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

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.: 31 AF XY: 0.0313 AC XY: 22760 AN XY: 726954

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.: 33 AF XY: 0.0838 AC XY: 6243 AN XY: 74456

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	16
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

Other links and lift over

dbSNP: rs860573; hg19: chr2-219846749; COSMIC: COSV55387591; COSMIC: COSV55387591;