5-39219513-T-C

Variant names:

• chr5-39219513-T-C
• rs6863066
• NM_001465.6:c.-98A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001465.6(FYB1):​c.-98A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 985,256 control chromosomes in the GnomAD database, including 329,478 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 0.68 (38068 hom., cov: 32)
  • Exomes 𝑓: 0.83 (291410 hom.)
• Consequence: FYB1 NM_001465.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 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.-98A>G		5_prime_UTR	Exon 1 of 19	NP_001456.3
	FYB1	NM_001349333.2		c.-438A>G		5_prime_UTR	Exon 1 of 20	NP_001336262.1	O15117-2
	FYB1	NM_018594.2		c.-169A>G		5_prime_UTR	Exon 1 of 19	NP_061064.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000512982.4	TSL:2 MANE Select	c.-98A>G		5_prime_UTR	Exon 1 of 19	ENSP00000425845.3	O15117-2
	FYB1	ENST00000351578.12	TSL:1	c.-98A>G		5_prime_UTR	Exon 1 of 18	ENSP00000316460.7	O15117-1
	FYB1	ENST00000506557.5	TSL:4	c.-438A>G		5_prime_UTR	Exon 1 of 3	ENSP00000421988.2	D6RAE8

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102894 AN: 152004 Hom.: 38061 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.832 AC: 693565 AN: 833132 Hom.: 291410 Cov.: 33 AF XY: 0.834 AC XY: 320697 AN XY: 384740

African (AFR) AF: 0.313 AC: 4939 AN: 15786

American (AMR) AF: 0.740 AC: 728 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 4229 AN: 5152

East Asian (EAS) AF: 0.564 AC: 2046 AN: 3630

South Asian (SAS) AF: 0.749 AC: 12322 AN: 16458

European-Finnish (FIN) AF: 0.849 AC: 248 AN: 292

Middle Eastern (MID) AF: 0.815 AC: 1320 AN: 1620

European-Non Finnish (NFE) AF: 0.848 AC: 646167 AN: 761910

Other (OTH) AF: 0.790 AC: 21566 AN: 27300

GnomAD4 genome AF: 0.677 AC: 102928 AN: 152124 Hom.: 38068 Cov.: 32 AF XY: 0.677 AC XY: 50374 AN XY: 74370

African (AFR) AF: 0.357 AC: 14805 AN: 41472

American (AMR) AF: 0.736 AC: 11249 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2829 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2881 AN: 5166

South Asian (SAS) AF: 0.730 AC: 3526 AN: 4828

European-Finnish (FIN) AF: 0.787 AC: 8347 AN: 10602

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.835 AC: 56778 AN: 67986

Other (OTH) AF: 0.720 AC: 1520 AN: 2110

Alfa AF: 0.784 Hom.: 59890

Bravo AF: 0.654

Asia WGS AF: 0.614 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.59
PhyloP100		0.053
PromoterAI		-0.047	Neutral
Mutation Taster		=298/2	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: rs6863066; hg19: chr5-39219615;