5-39119621-C-T

Variant names:

• chr5-39119621-C-T
• rs379707
• NM_001465.6:c.2152G>A

Variant summary

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

The NM_001465.6(FYB1):​c.2152G>A​(p.Val718Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V718F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FYB1 NM_001465.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 0 publications found

Genes affected

FYB1 (HGNC:4036): (FYN binding protein 1) The protein encoded by this gene is an adapter for the FYN protein and LCP2 signaling cascades in T-cells. The encoded protein is involved in platelet activation and controls the expression of interleukin-2. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

FYB1 Gene-Disease associations (from GenCC):

• thrombocytopenia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027353466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.2152G>A	p.Val718Ile	missense_variant	Exon 15 of 19	ENST00000512982.4	NP_001456.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000512982.4	c.2152G>A	p.Val718Ile	missense_variant	Exon 15 of 19	2	NM_001465.6	ENSP00000425845.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.26
DEOGEN2	Benign	0.046	T;.;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.080	.;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.027	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.55
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.040	N;.;.;N;N
REVEL	Benign	0.018
Sift	Benign	0.56	T;.;.;T;T
Sift4G	Benign	0.92	T;.;T;T;T
Polyphen		0.0	B;.;.;B;.
Vest4		0.024
MutPred		0.18		Gain of methylation at K676 (P = 0.0924);.;.;Gain of methylation at K676 (P = 0.0924);.;
MVP		0.21
ClinPred		0.022	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.021
gMVP		0.020
Mutation Taster		=98/2	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: rs379707; hg19: chr5-39119723;