5-39108220-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+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 1,516,690 control chromosomes in the GnomAD database, including 591,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (57179 hom., cov: 31)
  • Exomes 𝑓: 0.88 (534767 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.700

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=-0.9).
• BP6: Variant 5-39108220-A-G is Benign according to our data. Variant chr5-39108220-A-G is described in ClinVar as [Benign]. Clinvar id is 1267008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2467+11T>C		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2467+11T>C		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131551 AN: 151836 Hom.: 57146 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.871

GnomAD3 exomes AF: 0.881 AC: 137418 AN: 155994 Hom.: 60820 AF XY: 0.889 AC XY: 73116 AN XY: 82282

Gnomad AFR exome AF: 0.817

Gnomad AMR exome AF: 0.795

Gnomad ASJ exome AF: 0.937

Gnomad EAS exome AF: 0.817

Gnomad SAS exome AF: 0.955

Gnomad FIN exome AF: 0.939

Gnomad NFE exome AF: 0.883

Gnomad OTH exome AF: 0.881

GnomAD4 exome AF: 0.884 AC: 1206871 AN: 1364736 Hom.: 534767 Cov.: 30 AF XY: 0.887 AC XY: 597493 AN XY: 673706

Gnomad4 AFR exome AF: 0.811

Gnomad4 AMR exome AF: 0.799

Gnomad4 ASJ exome AF: 0.937

Gnomad4 EAS exome AF: 0.857

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.937

Gnomad4 NFE exome AF: 0.881

Gnomad4 OTH exome AF: 0.883

GnomAD4 genome AF: 0.866 AC: 131637 AN: 151954 Hom.: 57179 Cov.: 31 AF XY: 0.871 AC XY: 64732 AN XY: 74288

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.873

Alfa AF: 0.876 Hom.: 12484

Bravo AF: 0.851

Asia WGS AF: 0.897 AC: 3113 AN: 3472

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	-0.90
Cadd	Benign	0.023
Dann	Benign	0.65

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: rs430630; hg19: chr5-39108322;