Variant 1-56744234-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001004303.5(FYB2):c.1420G>T(p.Glu474Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,612,204 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0024 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0031 ( 22 hom. )

Consequence

FYB2
NM_001004303.5 stop_gained

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

FYB2 (HGNC:27295): (FYN binding protein 2) Involved in T cell receptor signaling pathway and cell adhesion mediated by integrin. Located in immunological synapse and membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

FYB2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB2	NM_001004303.5 linkuse as main transcript	c.1420G>T	p.Glu474Ter	stop_gained	10/20	ENST00000343433.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB2	ENST00000343433.7 linkuse as main transcript	c.1420G>T	p.Glu474Ter	stop_gained	10/20	1	NM_001004303.5	P1	Q5VWT5-1
FYB2	ENST00000484327.1 linkuse as main transcript	n.1662G>T		non_coding_transcript_exon_variant	7/14	2
FYB2	ENST00000493000.5 linkuse as main transcript	n.427G>T		non_coding_transcript_exon_variant	6/14	5

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

372

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00299

AC:

747

AN:

249876

Hom.:

AF XY:

0.00294

AC XY:

397

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000747

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00312

GnomAD4 exome

AF:

0.00312

AC:

4562

AN:

1460310

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2254

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000763

Gnomad4 ASJ exome

AF:

0.0367

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.00284

Gnomad4 OTH exome

AF:

0.00491

GnomAD4 genome

AF:

0.00245

AC:

372

AN:

151894

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00424

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00273

AC:

331

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00415

EpiControl

AF:

0.00338

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.32

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.24

MutationTaster

Benign

1.0

Vest4

0.23

GERP RS

2.4

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