rs4957796

Positions:

• chr5-109066439-T-C

Variant summary

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

The NM_005246.4(FER):​c.1924+19241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,198 control chromosomes in the GnomAD database, including 2,051 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 0.16 (2051 hom., cov: 32)
• Consequence: FER NM_005246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FER	NM_005246.4	c.1924+19241T>C		intron_variant		ENST00000281092.9	NP_005237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FER	ENST00000281092.9	c.1924+19241T>C		intron_variant		1	NM_005246.4	ENSP00000281092	P1
FER	ENST00000618353.1	c.817+19241T>C		intron_variant		1		ENSP00000484767
FER	ENST00000438717.6	c.691+19241T>C		intron_variant		2		ENSP00000394297
FER	ENST00000504143.6	c.*1395+19241T>C		intron_variant, NMD_transcript_variant		5		ENSP00000421951

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23804 AN: 152080 Hom.: 2051 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.156 AC: 23813 AN: 152198 Hom.: 2051 Cov.: 32 AF XY: 0.156 AC XY: 11588 AN XY: 74430

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.156

Alfa AF: 0.176 Hom.: 554

Bravo AF: 0.145

Asia WGS AF: 0.0980 AC: 339 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.86

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: rs4957796; hg19: chr5-108402140;