5-109062672-C-A

Variant names:

• chr5-109062672-C-A
• rs10491333
• NM_005246.4:c.1924+15474C>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FER	NM_005246.4	c.1924+15474C>A		intron_variant	Intron 16 of 19	ENST00000281092.9	NP_005237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FER	ENST00000281092.9	c.1924+15474C>A		intron_variant	Intron 16 of 19	1	NM_005246.4	ENSP00000281092.4
FER	ENST00000618353.1	c.817+15474C>A		intron_variant	Intron 7 of 10	1		ENSP00000484767.1
FER	ENST00000438717.6	c.691+15474C>A		intron_variant	Intron 7 of 10	2		ENSP00000394297.4
FER	ENST00000504143.6	n.*1395+15474C>A		intron_variant	Intron 14 of 17	5		ENSP00000421951.2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15287 AN: 151954 Hom.: 823 Cov.: 32

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.: 32 AF XY: 0.0982 AC XY: 7302 AN XY: 74332

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: 7 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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8703 AN: 67986

Other (OTH) AF: 0.102 AC: 214 AN: 2108

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.90
DANN	Benign	0.45
PhyloP100		-0.70
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: rs10491333; hg19: chr5-108398373;