rs379707

chr5-39119621-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.546

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	c.2152G>T	p.Val718Phe	missense_variant	15/19	2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86603 AN: 151720 Hom.: 27471 Cov.: 32

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

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.: 45 AF XY: 0.686 AC XY: 466204 AN XY: 679414

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.: 32 AF XY: 0.574 AC XY: 42591 AN XY: 74200

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	T
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	N
MetaRNN	Benign	0.0000030	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.34	T
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	T
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

Other links and lift over

dbSNP: rs379707; hg19: chr5-39119723; COSMIC: COSV60943087;