rs765947794

Variant names:

• chr15-90889521-G-A
• rs765947794
• NM_002005.4:c.811G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-90889521-G-A
• chr15-90889521-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002005.4(FES):​c.811G>A​(p.Ala271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FES NM_002005.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39
• Publications: 0 publications found

Genes affected

FES (HGNC:3657): (FES proto-oncogene, tyrosine kinase) This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01900509).
• BP6: Variant 15-90889521-G-A is Benign according to our data. Variant chr15-90889521-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3094495.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002005.4. 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
	FES	NM_002005.4	MANE Select	c.811G>A	p.Ala271Thr	missense	Exon 7 of 19	NP_001996.1	P07332-1
	FES	NM_001143783.1		c.637G>A	p.Ala213Thr	missense	Exon 5 of 17	NP_001137255.1	P07332-3
	FES	NM_001143784.1		c.811G>A	p.Ala271Thr	missense	Exon 6 of 17	NP_001137256.1	P07332-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FES	ENST00000328850.8	TSL:1 MANE Select	c.811G>A	p.Ala271Thr	missense	Exon 7 of 19	ENSP00000331504.3	P07332-1
	FES	ENST00000394300.7	TSL:1	c.637G>A	p.Ala213Thr	missense	Exon 5 of 17	ENSP00000377837.3	P07332-3
	FES	ENST00000444422.2	TSL:1	c.811G>A	p.Ala271Thr	missense	Exon 6 of 17	ENSP00000400868.2	P07332-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251138 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461600 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000357 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.063
DANN	Benign	0.42
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.75	N
REVEL	Benign	0.011
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.26		Gain of glycosylation at A271 (P = 0.0071)
MVP		0.42
MPC		0.31
ClinPred		0.0095	T
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.10
Mutation Taster		=91/9	polymorphism

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: rs765947794; hg19: chr15-91432751; COSMIC: COSV60997787; COSMIC: COSV60997787;