5-108897661-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005246.4(FER):c.1049T>C(p.Ile350Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000969 in 1,586,526 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

FER
NM_005246.4 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.54

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008577138).

BP6

Variant 5-108897661-T-C is Benign according to our data. Variant chr5-108897661-T-C is described in ClinVar as [Benign]. Clinvar id is 780559.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00524 (798/152318) while in subpopulation AFR AF= 0.0177 (736/41572). AF 95% confidence interval is 0.0166. There are 8 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FER	NM_005246.4 linkuse as main transcript	c.1049T>C	p.Ile350Thr	missense_variant, splice_region_variant	10/20	ENST00000281092.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER	ENST00000281092.9 linkuse as main transcript	c.1049T>C	p.Ile350Thr	missense_variant, splice_region_variant	10/20	1	NM_005246.4	P1	P16591-1
FER	ENST00000438717.6 linkuse as main transcript	c.-185T>C		5_prime_UTR_variant	1/11	2
FER	ENST00000504143.6 linkuse as main transcript	c.*520T>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	8/18	5

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

797

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

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:

0.0000882

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00132

AC:

300

AN:

226956

Hom.:

AF XY:

0.000998

AC XY:

123

AN XY:

123260

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000756

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.000516

AC:

740

AN:

1434208

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

325

AN XY:

712924

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000247

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000336

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.00524

AC:

798

AN:

152318

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.00601

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00150

AC:

182

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Benign

0.81

DEOGEN2

Benign

0.075

Eigen

Benign

-0.17

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.53

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.080

REVEL

Benign

0.16

Sift

Benign

0.69

Sift4G

Benign

0.61

Polyphen

0.094

Vest4

0.60

MVP

0.56

MPC

0.24

ClinPred

0.013

GERP RS

4.7

Varity_R

0.063

gMVP

0.093

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over