5-39119621-C-G

Variant names:

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

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>C​(p.Val718Leu) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=0.021131068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.2152G>C	p.Val718Leu	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>C	p.Val718Leu	missense_variant	Exon 15 of 19	2	NM_001465.6	ENSP00000425845.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1379580 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 680608

African (AFR) AF: 0.00 AC: 0 AN: 30946

American (AMR) AF: 0.00 AC: 0 AN: 30302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24242

East Asian (EAS) AF: 0.00 AC: 0 AN: 36614

South Asian (SAS) AF: 0.00 AC: 0 AN: 73888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071640

Other (OTH) AF: 0.00 AC: 0 AN: 56990

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.28
DANN	Benign	0.10
DEOGEN2	Benign	0.042	T;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.11	.;.;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.021	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.55
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.23	N;.;.;N;N
REVEL	Benign	0.029
Sift	Benign	0.72	T;.;.;T;T
Sift4G	Benign	1.0	T;.;T;T;T
Polyphen		0.0	B;.;.;B;.
Vest4		0.025
MutPred		0.12		Loss of methylation at K676 (P = 0.0721);.;.;Loss of methylation at K676 (P = 0.0721);.;
MVP		0.20
ClinPred		0.018	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.026
Mutation Taster		=97/3	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;