5-39119120-T-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.2239-84A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 629,782 control chromosomes in the GnomAD database, including 253,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (56369 hom., cov: 32)
  • Exomes 𝑓: 0.90 (196820 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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=-0.87).
• BP6: Variant 5-39119120-T-G is Benign according to our data. Variant chr5-39119120-T-G is described in ClinVar as [Benign]. Clinvar id is 1278517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2239-84A>C		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2239-84A>C		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129937 AN: 151960 Hom.: 56355 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.853

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.863

GnomAD4 exome AF: 0.904 AC: 431879 AN: 477702 Hom.: 196820 AF XY: 0.906 AC XY: 217476 AN XY: 240132

Gnomad4 AFR exome AF: 0.723

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.926

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.887

Gnomad4 FIN exome AF: 0.927

Gnomad4 NFE exome AF: 0.931

Gnomad4 OTH exome AF: 0.889

GnomAD4 genome AF: 0.855 AC: 129995 AN: 152080 Hom.: 56369 Cov.: 32 AF XY: 0.854 AC XY: 63500 AN XY: 74328

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.890

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.861

Alfa AF: 0.922 Hom.: 48471

Bravo AF: 0.843

Asia WGS AF: 0.747 AC: 2583 AN: 3456

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	-0.87
Cadd	Benign	0.17
Dann	Benign	0.66

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: rs427829; hg19: chr5-39119222; COSMIC: COSV60955409;