chr5-39191192-C-T

Variant names:

• chr5-39191192-C-T
• rs66782
• NM_001465.6:c.1135+10634G>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.1135+10634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,036 control chromosomes in the GnomAD database, including 32,610 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 0.65 (32610 hom., cov: 31)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 8 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 (AMR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.1135+10634G>A		intron_variant	Intron 2 of 18	ENST00000512982.4	NP_001456.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB1	ENST00000512982.4	c.1135+10634G>A		intron_variant	Intron 2 of 18	2	NM_001465.6	ENSP00000425845.3
FYB1	ENST00000351578.12	c.1135+10634G>A		intron_variant	Intron 2 of 17	1		ENSP00000316460.7
FYB1	ENST00000515010.5	c.1135+10634G>A		intron_variant	Intron 1 of 16	1		ENSP00000426346.1
FYB1	ENST00000646045.2	c.1165+10634G>A		intron_variant	Intron 2 of 18			ENSP00000493623.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98068 AN: 151918 Hom.: 32587 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.645 AC: 98138 AN: 152036 Hom.: 32610 Cov.: 31 AF XY: 0.645 AC XY: 47896 AN XY: 74294

African (AFR) AF: 0.490 AC: 20320 AN: 41436

American (AMR) AF: 0.729 AC: 11142 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2196 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2029 AN: 5160

South Asian (SAS) AF: 0.689 AC: 3319 AN: 4820

European-Finnish (FIN) AF: 0.716 AC: 7565 AN: 10568

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49541 AN: 67992

Other (OTH) AF: 0.631 AC: 1331 AN: 2108

Alfa AF: 0.698 Hom.: 166308

Bravo AF: 0.634

Asia WGS AF: 0.588 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.41
PhyloP100		-0.92
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: rs66782; hg19: chr5-39191294;