NM_005246.4:c.189T>C

Variant names:

• chr5-108798371-T-C
• rs56199104
• NM_005246.4:c.189T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005246.4(FER):​c.189T>C​(p.Tyr63Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,612,732 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (10 hom.)
• Consequence: FER NM_005246.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 5-108798371-T-C is Benign according to our data. Variant chr5-108798371-T-C is described in ClinVar as Benign. ClinVar VariationId is 791263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00525 (800/152350) while in subpopulation AFR AF = 0.0179 (744/41572). AF 95% confidence interval is 0.0168. There are 9 homozygotes in GnomAd4. There are 366 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 800 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FER	NM_005246.4	MANE Select	c.189T>C	p.Tyr63Tyr	synonymous	Exon 3 of 20	NP_005237.2	P16591-1
	FER	NM_001308038.2		c.189T>C	p.Tyr63Tyr	synonymous	Exon 4 of 8	NP_001294967.1
	FER	NM_001308028.2		c.-63T>C		5_prime_UTR	Exon 3 of 18	NP_001294957.1	P16591-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FER	ENST00000281092.9	TSL:1 MANE Select	c.189T>C	p.Tyr63Tyr	synonymous	Exon 3 of 20	ENSP00000281092.4	P16591-1
	FER	ENST00000502752.1	TSL:1	n.514T>C		non_coding_transcript_exon	Exon 4 of 8
	FER	ENST00000880768.1		c.189T>C	p.Tyr63Tyr	synonymous	Exon 3 of 20	ENSP00000550827.1

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 786 AN: 152232 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00134 AC: 337 AN: 250988 AF XY: 0.00101

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000609 AC: 890 AN: 1460382 Hom.: 10 Cov.: 30 AF XY: 0.000553 AC XY: 402 AN XY: 726552

African (AFR) AF: 0.0188 AC: 630 AN: 33428

American (AMR) AF: 0.00141 AC: 63 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00162 AC: 9 AN: 5558

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1111086

Other (OTH) AF: 0.00187 AC: 113 AN: 60300

GnomAD4 genome AF: 0.00525 AC: 800 AN: 152350 Hom.: 9 Cov.: 32 AF XY: 0.00491 AC XY: 366 AN XY: 74510

African (AFR) AF: 0.0179 AC: 744 AN: 41572

American (AMR) AF: 0.00255 AC: 39 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68038

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00385 Hom.: 0

Bravo AF: 0.00608

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.49
PhyloP100		1.3
Mutation Taster		=268/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs56199104; hg19: chr5-108134072;