5-39119142-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.2239-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 540,784 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (387 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (100 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.593

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=-0.84).
• BP6: Variant 5-39119142-A-G is Benign according to our data. Variant chr5-39119142-A-G is described in ClinVar as [Benign]. Clinvar id is 1239268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2239-106T>C		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2239-106T>C		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 5791 AN: 152112 Hom.: 385 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.00445 AC: 1730 AN: 388554 Hom.: 100 AF XY: 0.00391 AC XY: 770 AN XY: 197058

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0000928

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000299

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000339

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0382 AC: 5809 AN: 152230 Hom.: 387 Cov.: 33 AF XY: 0.0370 AC XY: 2757 AN XY: 74420

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0321

Alfa AF: 0.0221 Hom.: 52

Bravo AF: 0.0437

Asia WGS AF: 0.0110 AC: 38 AN: 3466

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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.60

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: rs16868122; hg19: chr5-39119244;