Genetic Variant FER:p.Leu284Val (chr5-108872139-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005246.4(FER):c.850C>G(p.Leu284Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000577 in 1,611,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

FER
NM_005246.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.111

Publications

0 publications found

Variant links:

Genes affected

FER (HGNC:3655): (FER tyrosine kinase) The protein encoded by this gene is a member of the FPS/FES family of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion and mediates signaling from the cell surface to the cytoskeleton via growth factor receptors. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Apr 2015]

FER links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18752918).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FER	NM_005246.4	MANE Select	c.850C>G	p.Leu284Val	missense	Exon 8 of 20	NP_005237.2	P16591-1
FER	NM_001308028.2		c.325C>G	p.Leu109Val	missense	Exon 6 of 18	NP_001294957.1	P16591-2
FER	NR_146155.2		n.955C>G		non_coding_transcript_exon	Exon 7 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FER	ENST00000281092.9	TSL:1 MANE Select	c.850C>G	p.Leu284Val	missense	Exon 8 of 20	ENSP00000281092.4	P16591-1
FER	ENST00000880768.1		c.850C>G	p.Leu284Val	missense	Exon 8 of 20	ENSP00000550827.1
FER	ENST00000880770.1		c.850C>G	p.Leu284Val	missense	Exon 7 of 19	ENSP00000550829.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000321

AC:

AN:

249058

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000583

AC:

AN:

1459194

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

725946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.0000903

AC:

AN:

44318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39444

South Asian (SAS)

AF:

0.00

AC:

AN:

85940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000684

AC:

AN:

1110706

Other (OTH)

AF:

0.0000830

AC:

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000526

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41534

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67916

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000565

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3470

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.033

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

PhyloP100

0.11

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.98

REVEL

Benign

0.22

Sift

Benign

0.42

Sift4G

Benign

0.47

Polyphen

0.91

Vest4

0.55

MVP

0.71

MPC

0.36

ClinPred

0.18

GERP RS

1.6

Varity_R

0.073

gMVP

0.37

Mutation Taster

=61/39

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over