Genetic Variant NM_001465.6:c.1922T>C (chr5-39126121-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001465.6(FYB1):c.1922T>C(p.Val641Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,613,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

FYB1
NM_001465.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.875

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032892615).

BP6

Variant 5-39126121-A-G is Benign according to our data. Variant chr5-39126121-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 435272.

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.1922T>C	p.Val641Ala	missense	Exon 12 of 19	NP_001456.3
FYB1	NM_001243093.2		c.1952T>C	p.Val651Ala	missense	Exon 12 of 19	NP_001230022.1	O15117-3
FYB1	NM_001349333.2		c.1922T>C	p.Val641Ala	missense	Exon 13 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.1922T>C	p.Val641Ala	missense	Exon 12 of 19	ENSP00000425845.3	O15117-2
FYB1	ENST00000351578.12	TSL:1	c.1907+1620T>C		intron	N/A	ENSP00000316460.7	O15117-1
FYB1	ENST00000515010.5	TSL:1	c.1907+1620T>C		intron	N/A	ENSP00000426346.1	O15117-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000258

AC:

AN:

248474

AF XY:

0.000237

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000497

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000424

AC:

619

AN:

1461134

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

286

AN XY:

726844

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33452

American (AMR)

AF:

0.000112

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000528

AC:

587

AN:

1111540

Other (OTH)

AF:

0.000265

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000217

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.000197

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.000292

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000362

AC:

ExAC

AF:

0.000306

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000297

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.93

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.58

M_CAP

Benign

0.0065

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.96

PhyloP100

0.88

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.18

REVEL

Benign

0.026

Sift

Benign

0.47

Sift4G

Benign

0.28

Vest4

0.18

MVP

0.37

ClinPred

0.051

GERP RS

-1.8

gMVP

0.10

Mutation Taster

=94/6

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

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