5-39124491-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001465.6(FYB1):c.2046-213T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,936 control chromosomes in the GnomAD database, including 8,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8472 hom., cov: 32)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-39124491-A-T is Benign according to our data. Variant chr5-39124491-A-T is described in ClinVar as [Benign]. Clinvar id is 1259044.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2046-213T>A		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2046-213T>A		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49895 AN: 151818 Hom.: 8442 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.329 AC: 49977 AN: 151936 Hom.: 8472 Cov.: 32 AF XY: 0.326 AC XY: 24231 AN XY: 74254

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.360

Alfa AF: 0.301 Hom.: 874

Bravo AF: 0.337

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2303806; hg19: chr5-39124593;