rs1549690

Variant names:

• chr5-39157692-A-C
• rs1549690
• NM_001465.6:c.1136-4088T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-39157692-A-C
• chr5-39157692-A-G

Variant summary

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

The NM_001465.6(FYB1):​c.1136-4088T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,098 control chromosomes in the GnomAD database, including 52,213 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 0.81 (52213 hom., cov: 32)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB1	NM_001465.6	c.1136-4088T>G		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.1136-4088T>G		intron_variant	Intron 2 of 18	2	NM_001465.6	ENSP00000425845.3
FYB1	ENST00000351578.12	c.1136-4088T>G		intron_variant	Intron 2 of 17	1		ENSP00000316460.7
FYB1	ENST00000515010.5	c.1136-4088T>G		intron_variant	Intron 1 of 16	1		ENSP00000426346.1
FYB1	ENST00000646045.2	c.1166-4088T>G		intron_variant	Intron 2 of 18			ENSP00000493623.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122994 AN: 151980 Hom.: 52208 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.809 AC: 123034 AN: 152098 Hom.: 52213 Cov.: 32 AF XY: 0.809 AC XY: 60148 AN XY: 74382

African (AFR) AF: 0.569 AC: 23571 AN: 41420

American (AMR) AF: 0.883 AC: 13493 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3227 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2005 AN: 5166

South Asian (SAS) AF: 0.860 AC: 4148 AN: 4822

European-Finnish (FIN) AF: 0.931 AC: 9863 AN: 10598

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64015 AN: 68020

Other (OTH) AF: 0.828 AC: 1749 AN: 2112

Alfa AF: 0.896 Hom.: 113720

Bravo AF: 0.789

Asia WGS AF: 0.644 AC: 2243 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	0.57
DANN	Benign	0.58
PhyloP100		-1.2
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: rs1549690; hg19: chr5-39157794;