rs4957798

Variant names:

• chr5-109108853-C-T
• rs4957798
• NM_005246.4:c.2048+8334C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005246.4(FER):​c.2048+8334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,078 control chromosomes in the GnomAD database, including 2,696 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 0.19 (2696 hom., cov: 32)
• Consequence: FER NM_005246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FER	NM_005246.4	c.2048+8334C>T		intron_variant	Intron 17 of 19	ENST00000281092.9	NP_005237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FER	ENST00000281092.9	c.2048+8334C>T		intron_variant	Intron 17 of 19	1	NM_005246.4	ENSP00000281092.4
FER	ENST00000618353.1	c.941+8334C>T		intron_variant	Intron 8 of 10	1		ENSP00000484767.1
FER	ENST00000438717.6	c.815+8334C>T		intron_variant	Intron 8 of 10	2		ENSP00000394297.4
FER	ENST00000504143.6	n.*1519+8334C>T		intron_variant	Intron 15 of 17	5		ENSP00000421951.2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28141 AN: 151960 Hom.: 2698 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.185 AC: 28153 AN: 152078 Hom.: 2696 Cov.: 32 AF XY: 0.181 AC XY: 13479 AN XY: 74368

African (AFR) AF: 0.201 AC: 8337 AN: 41478

American (AMR) AF: 0.126 AC: 1929 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3468

East Asian (EAS) AF: 0.0667 AC: 346 AN: 5184

South Asian (SAS) AF: 0.145 AC: 699 AN: 4816

European-Finnish (FIN) AF: 0.185 AC: 1953 AN: 10584

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13545 AN: 67968

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.211 Hom.: 3028

Bravo AF: 0.181

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.70
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4957798; hg19: chr5-108444554;