5-39247407-G-C

Variant names:

• chr5-39247407-G-C
• rs28523355
• NM_001243093.2:c.3+23162C>G

Variant summary

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

The NM_001243093.2(FYB1):​c.3+23162C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,700 control chromosomes in the GnomAD database, including 5,744 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 (5744 hom., cov: 29)
• Consequence: FYB1 NM_001243093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• 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=-0.95).
• 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.3+23162C>G		intron	N/A	NP_001230022.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYB1	ENST00000646045.2		c.3+23162C>G		intron	N/A	ENSP00000493623.1
	FYB1	ENST00000510188.1	TSL:3	c.-28+26996C>G		intron	N/A	ENSP00000426597.1
	FYB1	ENST00000512138.1	TSL:3	c.-28+3264C>G		intron	N/A	ENSP00000424919.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25459 AN: 151580 Hom.: 5728 Cov.: 29

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00500

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.168 AC: 25527 AN: 151700 Hom.: 5744 Cov.: 29 AF XY: 0.169 AC XY: 12549 AN XY: 74150

African (AFR) AF: 0.496 AC: 20510 AN: 41320

American (AMR) AF: 0.116 AC: 1771 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3456

East Asian (EAS) AF: 0.301 AC: 1545 AN: 5136

South Asian (SAS) AF: 0.169 AC: 812 AN: 4802

European-Finnish (FIN) AF: 0.0202 AC: 212 AN: 10518

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00499 AC: 339 AN: 67940

Other (OTH) AF: 0.134 AC: 282 AN: 2100

Alfa AF: 0.00935 Hom.: 22

Bravo AF: 0.192

Asia WGS AF: 0.238 AC: 827 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.0070
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: rs28523355; hg19: chr5-39247509;