Genetic Variant NM_001465.6:c.2152G>C (chr5-39119621-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.546

Publications

0 publications found

Variant links:

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)

FYB1 links:

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ACMG classification

Classification was made for transcript

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001465.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FYB1	NM_001465.6	MANE Select	c.2152G>C	p.Val718Leu	missense	Exon 15 of 19	NP_001456.3
FYB1	NM_001243093.2		c.2182G>C	p.Val728Leu	missense	Exon 15 of 19	NP_001230022.1
FYB1	NM_001349333.2		c.2152G>C	p.Val718Leu	missense	Exon 16 of 20	NP_001336262.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FYB1	ENST00000512982.4	TSL:2 MANE Select	c.2152G>C	p.Val718Leu	missense	Exon 15 of 19	ENSP00000425845.3
FYB1	ENST00000351578.12	TSL:1	c.2014G>C	p.Val672Leu	missense	Exon 14 of 18	ENSP00000316460.7
FYB1	ENST00000515010.5	TSL:1	c.2014G>C	p.Val672Leu	missense	Exon 13 of 17	ENSP00000426346.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1379580

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680608

African (AFR)

AF:

0.00

AC:

AN:

30946

American (AMR)

AF:

0.00

AC:

AN:

30302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24242

East Asian (EAS)

AF:

0.00

AC:

AN:

36614

South Asian (SAS)

AF:

0.00

AC:

AN:

73888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5550

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071640

Other (OTH)

AF:

0.00

AC:

AN:

56990

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.28

(source)

DANN

Benign

0.10

DEOGEN2

Benign

0.042

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.11

M_CAP

Benign

0.013

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.0

PhyloP100

-0.55

PrimateAI

Benign

0.33

PROVEAN

Benign

0.23

REVEL

Benign

0.029

Sift

Benign

0.72

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.025

MutPred

0.12

Loss of methylation at K676 (P = 0.0721)

MVP

0.20

ClinPred

0.018

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

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over