5-39105492-C-T

Variant names:

• chr5-39105492-C-T
• rs358501
• NM_001465.6:c.*1951G>A

Variant summary

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

The NM_001465.6(FYB1):​c.*1951G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,010 control chromosomes in the GnomAD database, including 49,355 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 0.80 (49355 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: FYB1 NM_001465.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.*1951G>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000512982.4	NP_001456.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000512982.4	c.*1951G>A		3_prime_UTR_variant	Exon 19 of 19	2	NM_001465.6	ENSP00000425845.3
FYB1	ENST00000351578.12	c.*1951G>A		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000316460.7
FYB1	ENST00000646045.2	c.*1951G>A		3_prime_UTR_variant	Exon 19 of 19			ENSP00000493623.1

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122229 AN: 151892 Hom.: 49305 Cov.: 30

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.796

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.805 AC: 122341 AN: 152010 Hom.: 49355 Cov.: 30 AF XY: 0.805 AC XY: 59800 AN XY: 74270

African (AFR) AF: 0.806 AC: 33405 AN: 41456

American (AMR) AF: 0.801 AC: 12218 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2950 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3183 AN: 5156

South Asian (SAS) AF: 0.838 AC: 4033 AN: 4812

European-Finnish (FIN) AF: 0.810 AC: 8543 AN: 10548

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55290 AN: 67994

Other (OTH) AF: 0.796 AC: 1682 AN: 2112

Alfa AF: 0.809 Hom.: 80088

Bravo AF: 0.802

Asia WGS AF: 0.782 AC: 2715 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		0.28
Mutation Taster		=100/0	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: rs358501; hg19: chr5-39105594;