5-39124406-C-T

Position:

• chr5-39124406-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001465.6(FYB1):​c.2046-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 524,384 control chromosomes in the GnomAD database, including 38,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16929 hom., cov: 32)
  • Exomes 𝑓: 0.32 (21377 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.861

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-39124406-C-T is Benign according to our data. Variant chr5-39124406-C-T is described in ClinVar as [Benign]. Clinvar id is 1180183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2046-128G>A		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2046-128G>A		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65429 AN: 151908 Hom.: 16877 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.324 AC: 120761 AN: 372356 Hom.: 21377 AF XY: 0.321 AC XY: 62215 AN XY: 193804

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.543

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.362

GnomAD4 genome AF: 0.431 AC: 65537 AN: 152028 Hom.: 16929 Cov.: 32 AF XY: 0.427 AC XY: 31760 AN XY: 74318

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.435

Alfa AF: 0.369 Hom.: 1978

Bravo AF: 0.455

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.52

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: rs2303807; hg19: chr5-39124508; COSMIC: COSV60947999; COSMIC: COSV60947999;