Genetic Variant NM_001465.6:c.2468G>A (chr5-39107465-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001465.6(FYB1):c.2468G>A(p.Gly823Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000529 in 1,512,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

FYB1
NM_001465.6 missense, splice_region

Scores

Splicing: ADA: 0.001684

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

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: Labcorp Genetics (formerly Invitae), ClinGen

FYB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121941924).

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	UniProt
FYB1	NM_001465.6	MANE Select	c.2468G>A	p.Gly823Asp	missense splice_region	Exon 19 of 19	NP_001456.3
FYB1	NM_001243093.2		c.2498G>A	p.Gly833Asp	missense splice_region	Exon 19 of 19	NP_001230022.1	O15117-3
FYB1	NM_001349333.2		c.2468G>A	p.Gly823Asp	missense splice_region	Exon 20 of 20	NP_001336262.1	O15117-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FYB1	ENST00000512982.4	TSL:2 MANE Select	c.2468G>A	p.Gly823Asp	missense splice_region	Exon 19 of 19	ENSP00000425845.3	O15117-2
FYB1	ENST00000351578.12	TSL:1	c.2330G>A	p.Gly777Asp	missense splice_region	Exon 18 of 18	ENSP00000316460.7	O15117-1
FYB1	ENST00000515010.5	TSL:1	c.2330G>A	p.Gly777Asp	missense splice_region	Exon 17 of 17	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000666

AC:

AN:

150162

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000441

AC:

AN:

1361372

Hom.:

Cov.:

AF XY:

0.00000447

AC XY:

AN XY:

671086

show subpopulations

African (AFR)

AF:

0.0000658

AC:

AN:

30380

American (AMR)

AF:

0.00

AC:

AN:

33678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24402

East Asian (EAS)

AF:

0.00

AC:

AN:

34532

South Asian (SAS)

AF:

0.00

AC:

AN:

71382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48492

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00000379

AC:

AN:

1056724

Other (OTH)

AF:

0.00

AC:

AN:

56238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151588

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73950

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41296

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67816

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.00000933

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.068

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Benign

0.0079

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

1.6

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.86

REVEL

Benign

0.15

Sift

Benign

0.93

Sift4G

Benign

1.0

Polyphen

0.27

Vest4

0.23

MVP

0.44

ClinPred

0.20

GERP RS

4.4

Varity_R

0.096

gMVP

0.19

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0017

dbscSNV1_RF

Benign

0.23

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over