5-39108207-A-G

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.2467+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,498,552 control chromosomes in the GnomAD database, including 451,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (42093 hom., cov: 31)
  • Exomes 𝑓: 0.78 (409336 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169

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=-0.89).
• BP6: Variant 5-39108207-A-G is Benign according to our data. Variant chr5-39108207-A-G is described in ClinVar as [Benign]. Clinvar id is 1230439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2467+24T>C		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2467+24T>C		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112503 AN: 151744 Hom.: 42066 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.748

GnomAD3 exomes AF: 0.766 AC: 119254 AN: 155678 Hom.: 46090 AF XY: 0.772 AC XY: 63444 AN XY: 82142

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.731

Gnomad ASJ exome AF: 0.823

Gnomad EAS exome AF: 0.592

Gnomad SAS exome AF: 0.837

Gnomad FIN exome AF: 0.794

Gnomad NFE exome AF: 0.783

Gnomad OTH exome AF: 0.773

GnomAD4 exome AF: 0.778 AC: 1047571 AN: 1346690 Hom.: 409336 Cov.: 26 AF XY: 0.780 AC XY: 519115 AN XY: 665658

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.815

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.767

GnomAD4 genome AF: 0.741 AC: 112587 AN: 151862 Hom.: 42093 Cov.: 31 AF XY: 0.745 AC XY: 55273 AN XY: 74222

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.749

Alfa AF: 0.769 Hom.: 9248

Bravo AF: 0.731

Asia WGS AF: 0.769 AC: 2667 AN: 3470

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

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.8
Dann	Benign	0.37

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: rs377022; hg19: chr5-39108309; COSMIC: COSV60950372;