Variant 5-39119621-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001465.6(FYB1):c.2152G>T(p.Val718Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,529,164 control chromosomes in the GnomAD database, including 354,831 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27475 hom., cov: 32)

Exomes 𝑓: 0.68 ( 327356 hom. )

Consequence

FYB1
NM_001465.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.546

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9638313E-6).

BP6

Variant 5-39119621-C-A is Benign according to our data. Variant chr5-39119621-C-A is described in ClinVar as [Benign]. Clinvar id is 1280849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6 linkuse as main transcript	c.2152G>T	p.Val718Phe	missense_variant	15/19	ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4 linkuse as main transcript	c.2152G>T	p.Val718Phe	missense_variant	15/19	2	NM_001465.6	P4	O15117-2

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86603

AN:

151720

Hom.:

27471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.568

GnomAD3 exomes

AF:

0.627

AC:

93896

AN:

149714

Hom.:

30996

AF XY:

0.636

AC XY:

50013

AN XY:

78586

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.657

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.713

Gnomad NFE exome

AF:

0.683

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.684

AC:

941974

AN:

1377328

Hom.:

327356

Cov.:

AF XY:

0.686

AC XY:

466204

AN XY:

679414

show subpopulations

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.717

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.643

GnomAD4 genome

AF:

0.570

AC:

86615

AN:

151836

Hom.:

27475

Cov.:

AF XY:

0.574

AC XY:

42591

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.651

Gnomad4 ASJ

AF:

0.628

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.720

Gnomad4 FIN

AF:

0.716

Gnomad4 NFE

AF:

0.708

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.672

Hom.:

69111

Bravo

AF:

0.547

TwinsUK

AF:

0.708

AC:

2624

ALSPAC

AF:

0.710

AC:

2736

ESP6500AA

AF:

0.278

AC:

996

ESP6500EA

AF:

0.691

AC:

5575

ExAC

AF:

0.531

AC:

55814

Asia WGS

AF:

0.570

AC:

1970

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.94

DANN

Benign

0.11

DEOGEN2

Benign

0.077

T;.;.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.079

.;.;T;T;T

MetaRNN

Benign

0.0000030

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.44

N;.;.;N;N

REVEL

Benign

0.021

Sift

Benign

0.73

T;.;.;T;T

Sift4G

Benign

0.34

T;.;T;T;T

Polyphen

0.0

B;.;.;B;.

Vest4

0.050

ClinPred

0.0016

GERP RS

-2.2

Varity_R

0.037

gMVP

0.041

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over