NM_001243093.2:c.4-32745G>A

Variant names:

• chr5-39235732-C-T
• rs1631837
• NM_001243093.2:c.4-32745G>A

Variant summary

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

The NM_001243093.2(FYB1):​c.4-32745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,864 control chromosomes in the GnomAD database, including 5,756 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 0.17 (5756 hom., cov: 31)
• Consequence: FYB1 NM_001243093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 0 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: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243093.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	NM_001243093.2		c.4-32745G>A		intron	N/A	NP_001230022.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000646045.2		c.4-32745G>A		intron	N/A	ENSP00000493623.1
	FYB1	ENST00000510188.1	TSL:3	c.-27-32745G>A		intron	N/A	ENSP00000426597.1
	FYB1	ENST00000512138.1	TSL:3	c.-28+14939G>A		intron	N/A	ENSP00000424919.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25536 AN: 151746 Hom.: 5741 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25602 AN: 151864 Hom.: 5756 Cov.: 31 AF XY: 0.169 AC XY: 12562 AN XY: 74214

African (AFR) AF: 0.496 AC: 20535 AN: 41374

American (AMR) AF: 0.120 AC: 1825 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1528 AN: 5142

South Asian (SAS) AF: 0.169 AC: 812 AN: 4812

European-Finnish (FIN) AF: 0.0205 AC: 217 AN: 10584

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.00505 AC: 343 AN: 67942

Other (OTH) AF: 0.136 AC: 286 AN: 2106

Alfa AF: 0.113 Hom.: 520

Bravo AF: 0.193

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1631837; hg19: chr5-39235834;