chr5-39119621-C-A

Variant names:

• chr5-39119621-C-A
• rs379707
• NM_001465.6:c.2152G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 14/20 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.546
• Publications: 37 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1280849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	NM_001465.6	MANE Select	c.2152G>T	p.Val718Phe	missense	Exon 15 of 19	NP_001456.3
	FYB1	NM_001243093.2		c.2182G>T	p.Val728Phe	missense	Exon 15 of 19	NP_001230022.1	O15117-3
	FYB1	NM_001349333.2		c.2152G>T	p.Val718Phe	missense	Exon 16 of 20	NP_001336262.1	O15117-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000512982.4	TSL:2 MANE Select	c.2152G>T	p.Val718Phe	missense	Exon 15 of 19	ENSP00000425845.3	O15117-2
	FYB1	ENST00000351578.12	TSL:1	c.2014G>T	p.Val672Phe	missense	Exon 14 of 18	ENSP00000316460.7	O15117-1
	FYB1	ENST00000515010.5	TSL:1	c.2014G>T	p.Val672Phe	missense	Exon 13 of 17	ENSP00000426346.1	O15117-1

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

GnomAD2 exomes AF: 0.627 AC: 93896 AN: 149714 AF XY: 0.636

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 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

African (AFR) AF: 0.256 AC: 7922 AN: 30892

American (AMR) AF: 0.658 AC: 19803 AN: 30092

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 14863 AN: 24162

East Asian (EAS) AF: 0.434 AC: 15832 AN: 36516

South Asian (SAS) AF: 0.717 AC: 52830 AN: 73632

European-Finnish (FIN) AF: 0.715 AC: 35254 AN: 49296

Middle Eastern (MID) AF: 0.637 AC: 3532 AN: 5542

European-Non Finnish (NFE) AF: 0.706 AC: 755338 AN: 1070300

Other (OTH) AF: 0.643 AC: 36600 AN: 56896

GnomAD4 genome AF: 0.570 AC: 86615 AN: 151836 Hom.: 27475 Cov.: 32 AF XY: 0.574 AC XY: 42591 AN XY: 74200

African (AFR) AF: 0.277 AC: 11477 AN: 41430

American (AMR) AF: 0.651 AC: 9936 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2175 AN: 3466

East Asian (EAS) AF: 0.401 AC: 2077 AN: 5176

South Asian (SAS) AF: 0.720 AC: 3467 AN: 4816

European-Finnish (FIN) AF: 0.716 AC: 7521 AN: 10504

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48041 AN: 67878

Other (OTH) AF: 0.567 AC: 1191 AN: 2102

Alfa AF: 0.663 Hom.: 128766

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.079	T
MetaRNN	Benign	0.0000030	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.55
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.021
Sift	Benign	0.73	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.050
ClinPred		0.0016	T
GERP RS		-2.2
Varity_R		0.037
gMVP		0.041
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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