rs835186

Variant names:

• chr5-39247525-A-T
• rs835186
• NM_001243093.2:c.3+23044T>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.3+23044T>A 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 152,056 control chromosomes in the GnomAD database, including 5,745 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 (5745 hom., cov: 29)
• Consequence: FYB1 NM_001243093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001243093.2	c.3+23044T>A		intron_variant	Intron 1 of 18		NP_001230022.1
FYB1	XM_047417071.1	c.-133+23044T>A		intron_variant	Intron 1 of 20		XP_047273027.1
FYB1	XM_006714464.4	c.-28+26878T>A		intron_variant	Intron 1 of 18		XP_006714527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000646045.2	c.3+23044T>A		intron_variant	Intron 1 of 18			ENSP00000493623.1
FYB1	ENST00000510188.1	c.-28+26878T>A		intron_variant	Intron 1 of 1	3		ENSP00000426597.1
FYB1	ENST00000512138.1	c.-28+3146T>A		intron_variant	Intron 2 of 2	3		ENSP00000424919.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25495 AN: 151938 Hom.: 5730 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: 0.168

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00503

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.168 AC: 25561 AN: 152056 Hom.: 5745 Cov.: 29 AF XY: 0.169 AC XY: 12573 AN XY: 74372

African (AFR) AF: 0.496 AC: 20520 AN: 41400

American (AMR) AF: 0.116 AC: 1775 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3466

East Asian (EAS) AF: 0.301 AC: 1554 AN: 5160

South Asian (SAS) AF: 0.168 AC: 811 AN: 4816

European-Finnish (FIN) AF: 0.0205 AC: 218 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00501 AC: 341 AN: 68006

Other (OTH) AF: 0.135 AC: 286 AN: 2112

Alfa AF: 0.0987 Hom.: 424

Bravo AF: 0.192

Asia WGS AF: 0.239 AC: 827 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.75
PhyloP100		-0.069
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: rs835186; hg19: chr5-39247627;