rs13177718

Positions:

• chr5-108777643-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005246.4(FER):​c.-60+9405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,198 control chromosomes in the GnomAD database, including 285 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 0.051 (285 hom., cov: 32)
• Consequence: FER NM_005246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER	NM_005246.4	c.-60+9405C>T		intron_variant		ENST00000281092.9	NP_005237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER	ENST00000281092.9	c.-60+9405C>T		intron_variant		1	NM_005246.4	ENSP00000281092	P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7724 AN: 152080 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0653

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0508 AC: 7725 AN: 152198 Hom.: 285 Cov.: 32 AF XY: 0.0491 AC XY: 3652 AN XY: 74420

Gnomad4 AFR AF: 0.0139

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0658

Gnomad4 FIN AF: 0.0498

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0698 Hom.: 577

Bravo AF: 0.0489

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs13177718; hg19: chr5-108113344;