dbSNP rs2161612: FYB1:c.*445T>C (chr5-39106998-A-G) – 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.*445T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,110 control chromosomes in the GnomAD database, including 8,142 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 0.31 ( 8127 hom., cov: 32)

Exomes 𝑓: 0.33 ( 15 hom. )

Consequence

FYB1
NM_001465.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.390

Publications

7 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
FYB1	NM_001465.6	MANE Select	c.*445T>C	3_prime_UTR	Exon 19 of 19	NP_001456.3
FYB1	NM_001243093.2		c.*445T>C	3_prime_UTR	Exon 19 of 19	NP_001230022.1	O15117-3
FYB1	NM_001349333.2		c.*445T>C	3_prime_UTR	Exon 20 of 20	NP_001336262.1	O15117-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FYB1	ENST00000512982.4	TSL:2 MANE Select	c.*445T>C	3_prime_UTR	Exon 19 of 19	ENSP00000425845.3	O15117-2
FYB1	ENST00000351578.12	TSL:1	c.*445T>C	3_prime_UTR	Exon 18 of 18	ENSP00000316460.7	O15117-1
FYB1	ENST00000646045.2		c.*445T>C	3_prime_UTR	Exon 19 of 19	ENSP00000493623.1	O15117-3

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47017

AN:

151780

Hom.:

8129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.330

AC:

AN:

212

Hom.:

Cov.:

AF XY:

0.402

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.357

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.362

AC:

AN:

152

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.310

AC:

47014

AN:

151898

Hom.:

8127

Cov.:

AF XY:

0.310

AC XY:

23008

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.172

AC:

7124

AN:

41504

American (AMR)

AF:

0.346

AC:

5278

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1276

AN:

3464

East Asian (EAS)

AF:

0.143

AC:

742

AN:

5180

South Asian (SAS)

AF:

0.237

AC:

1143

AN:

4824

European-Finnish (FIN)

AF:

0.391

AC:

4123

AN:

10548

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26418

AN:

67816

Other (OTH)

AF:

0.283

AC:

595

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1568

3137

4705

6274

7842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.364

Hom.:

6514

Bravo

AF:

0.298

Asia WGS

AF:

0.181

AC:

624

AN:

3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

(source)

DANN

Benign

0.75

PhyloP100

0.39

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over