rs835189

Variant names:

• chr5-39247992-C-T
• rs835189
• NM_001243093.2:c.3+22577G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243093.2(FYB1):​c.3+22577G>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 151,776 control chromosomes in the GnomAD database, including 5,724 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 (5724 hom., cov: 31)
• Consequence: FYB1 NM_001243093.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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+22577G>A		intron_variant	Intron 1 of 18		NP_001230022.1
FYB1	XM_047417071.1	c.-133+22577G>A		intron_variant	Intron 1 of 20		XP_047273027.1
FYB1	XM_006714464.4	c.-28+26411G>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+22577G>A		intron_variant	Intron 1 of 18			ENSP00000493623.1
FYB1	ENST00000510188.1	c.-28+26411G>A		intron_variant	Intron 1 of 1	3		ENSP00000426597.1
FYB1	ENST00000512138.1	c.-28+2679G>A		intron_variant	Intron 2 of 2	3		ENSP00000424919.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25421 AN: 151658 Hom.: 5709 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0637

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: 25487 AN: 151776 Hom.: 5724 Cov.: 31 AF XY: 0.169 AC XY: 12535 AN XY: 74170

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.00502

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0986 Hom.: 424

Bravo AF: 0.192

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs835189; hg19: chr5-39248094;