Genetic Variant NM_001465.6:c.-98A>G (chr5-39219513-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001465.6(FYB1):c.-98A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 985,256 control chromosomes in the GnomAD database, including 329,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 38068 hom., cov: 32)

Exomes 𝑓: 0.83 ( 291410 hom. )

Consequence

FYB1
NM_001465.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0530

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6 link	c.-98A>G		5_prime_UTR_variant	Exon 1 of 19	ENST00000512982.4	NP_001456.3	O15117-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000512982.4 link	c.-98A>G		5_prime_UTR_variant	Exon 1 of 19	2	NM_001465.6	ENSP00000425845.3		O15117-2

Frequencies

GnomAD3 genomes

AF:

0.677

AC:

102894

AN:

152004

Hom.:

38061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.843

Gnomad AMR

AF:

0.736

Gnomad ASJ

AF:

0.815

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.787

Gnomad MID

AF:

0.774

Gnomad NFE

AF:

0.835

Gnomad OTH

AF:

0.723

GnomAD4 exome

AF:

0.832

AC:

693565

AN:

833132

Hom.:

291410

Cov.:

AF XY:

0.834

AC XY:

320697

AN XY:

384740

show subpopulations

African (AFR)

AF:

0.313

AC:

4939

AN:

15786

American (AMR)

AF:

0.740

AC:

728

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

4229

AN:

5152

East Asian (EAS)

AF:

0.564

AC:

2046

AN:

3630

South Asian (SAS)

AF:

0.749

AC:

12322

AN:

16458

European-Finnish (FIN)

AF:

0.849

AC:

248

AN:

292

Middle Eastern (MID)

AF:

0.815

AC:

1320

AN:

1620

European-Non Finnish (NFE)

AF:

0.848

AC:

646167

AN:

761910

Other (OTH)

AF:

0.790

AC:

21566

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6238

12475

18713

24950

31188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19694

39388

59082

78776

98470

<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:

0.677

AC:

102928

AN:

152124

Hom.:

38068

Cov.:

AF XY:

0.677

AC XY:

50374

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.357

AC:

14805

AN:

41472

American (AMR)

AF:

0.736

AC:

11249

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

2829

AN:

3472

East Asian (EAS)

AF:

0.558

AC:

2881

AN:

5166

South Asian (SAS)

AF:

0.730

AC:

3526

AN:

4828

European-Finnish (FIN)

AF:

0.787

AC:

8347

AN:

10602

Middle Eastern (MID)

AF:

0.774

AC:

226

AN:

292

European-Non Finnish (NFE)

AF:

0.835

AC:

56778

AN:

67986

Other (OTH)

AF:

0.720

AC:

1520

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1371

2742

4113

5484

6855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.784

Hom.:

59890

Bravo

AF:

0.654

Asia WGS

AF:

0.614

AC:

2139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.8

(source)

DANN

Benign

0.59

PhyloP100

0.053

PromoterAI

-0.047

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over