Genetic Variant FER:c.1924+15474C>A (chr5-109062672-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005246.4(FER):c.1924+15474C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,072 control chromosomes in the GnomAD database, including 822 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 0.10 ( 822 hom., cov: 32)

Consequence

FER
NM_005246.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.698

Publications

3 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:

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new If you want to explore the variant's impact on the transcript NM_005246.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
FER	NM_005246.4	MANE Select	c.1924+15474C>A	intron	N/A	NP_005237.2	P16591-1
FER	NM_001308028.2		c.1399+15474C>A	intron	N/A	NP_001294957.1	P16591-2
FER	NM_001308031.2		c.817+15474C>A	intron	N/A	NP_001294960.1	P16591-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FER	ENST00000281092.9	TSL:1 MANE Select	c.1924+15474C>A	intron	N/A	ENSP00000281092.4	P16591-1
FER	ENST00000618353.1	TSL:1	c.817+15474C>A	intron	N/A	ENSP00000484767.1	P16591-3
FER	ENST00000880768.1		c.1924+15474C>A	intron	N/A	ENSP00000550827.1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15287

AN:

151954

Hom.:

823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0695

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0752

Gnomad FIN

AF:

0.0913

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.100

AC:

15280

AN:

152072

Hom.:

822

Cov.:

AF XY:

0.0982

AC XY:

7302

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0693

AC:

2877

AN:

41494

American (AMR)

AF:

0.105

AC:

1606

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

421

AN:

3464

East Asian (EAS)

AF:

0.00135

AC:

AN:

5188

South Asian (SAS)

AF:

0.0750

AC:

362

AN:

4826

European-Finnish (FIN)

AF:

0.0913

AC:

962

AN:

10542

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8703

AN:

67986

Other (OTH)

AF:

0.102

AC:

214

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

670

1339

2009

2678

3348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.116

Hom.:

565

Bravo

AF:

0.0981

Asia WGS

AF:

0.0310

AC:

110

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.90

(source)

DANN

Benign

0.45

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over