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GeneBe

5-108959248-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_005246.4(FER):c.1557T>C(p.Thr519=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,611,680 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 22 hom., cov: 32)
Exomes 𝑓: 0.00094 ( 20 hom. )

Consequence

FER
NM_005246.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-108959248-T-C is Benign according to our data. Variant chr5-108959248-T-C is described in ClinVar as [Benign]. Clinvar id is 792007.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.25 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1544/151972) while in subpopulation AFR AF= 0.0355 (1473/41536). AF 95% confidence interval is 0.034. There are 22 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1541 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FERNM_005246.4 linkuse as main transcriptc.1557T>C p.Thr519= synonymous_variant 13/20 ENST00000281092.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FERENST00000281092.9 linkuse as main transcriptc.1557T>C p.Thr519= synonymous_variant 13/201 NM_005246.4 P1P16591-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1541
AN:
151854
Hom.:
22
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0355
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00315
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000133
Gnomad OTH
AF:
0.00624
GnomAD3 exomes
AF:
0.00257
AC:
643
AN:
250200
Hom.:
16
AF XY:
0.00183
AC XY:
247
AN XY:
135298
show subpopulations
Gnomad AFR exome
AF:
0.0361
Gnomad AMR exome
AF:
0.00140
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:
0.0000442
Gnomad OTH exome
AF:
0.000985
GnomAD4 exome
AF:
0.000945
AC:
1379
AN:
1459708
Hom.:
20
Cov.:
30
AF XY:
0.000793
AC XY:
576
AN XY:
726156
show subpopulations
Gnomad4 AFR exome
AF:
0.0353
Gnomad4 AMR exome
AF:
0.00126
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000349
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.00174
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0102
AC:
1544
AN:
151972
Hom.:
22
Cov.:
32
AF XY:
0.00980
AC XY:
728
AN XY:
74282
show subpopulations
Gnomad4 AFR
AF:
0.0355
Gnomad4 AMR
AF:
0.00315
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000133
Gnomad4 OTH
AF:
0.00617
Alfa
AF:
0.00491
Hom.:
5
Bravo
AF:
0.0113
Asia WGS
AF:
0.00116
AC:
4
AN:
3474
EpiCase
AF:
0.0000548
EpiControl
AF:
0.000119

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 submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
Cadd
Benign
8.7
Dann
Benign
0.70

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.

Other links and lift over

dbSNP: rs34320303; hg19: chr5-108294949; API