5-108867763-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005246.4(FER):c.482-3dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,589,370 control chromosomes in the GnomAD database, including 33 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (31 hom., cov: 30)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: FER NM_005246.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268

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 -10 ACMG points.

• BP6: Variant 5-108867763-T-TC is Benign according to our data. Variant chr5-108867763-T-TC is described in ClinVar as [Benign]. Clinvar id is 719488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1839/150586) while in subpopulation AFR AF= 0.0426 (1731/40680). AF 95% confidence interval is 0.0409. There are 31 homozygotes in gnomad4. There are 844 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 1835 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FER	NM_005246.4	c.482-3dup		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000281092.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FER	ENST00000281092.9	c.482-3dup		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005246.4	P1
FER	ENST00000504143.6	c.208-3dup		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1835 AN: 150478 Hom.: 31 Cov.: 30

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00482

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00978

GnomAD3 exomes AF: 0.00276 AC: 626 AN: 227112 Hom.: 6 AF XY: 0.00179 AC XY: 220 AN XY: 123024

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000104

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.00101 AC: 1460 AN: 1438784 Hom.: 2 Cov.: 34 AF XY: 0.000865 AC XY: 619 AN XY: 715374

Gnomad4 AFR exome AF: 0.0379

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000497

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000452

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.0122 AC: 1839 AN: 150586 Hom.: 31 Cov.: 30 AF XY: 0.0115 AC XY: 844 AN XY: 73602

Gnomad4 AFR AF: 0.0426

Gnomad4 AMR AF: 0.00482

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000177

Gnomad4 OTH AF: 0.00967

Alfa AF: 0.000319 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs71224888; hg19: chr5-108203464;