5-39107251-T-A

Position:

• chr5-39107251-T-A

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.*192A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 388,254 control chromosomes in the GnomAD database, including 110,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40953 hom., cov: 32)
  • Exomes 𝑓: 0.76 (69122 hom.)
• Consequence: FYB1 NM_001465.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.42

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=-0.87).
• BP6: Variant 5-39107251-T-A is Benign according to our data. Variant chr5-39107251-T-A is described in ClinVar as [Benign]. Clinvar id is 1182755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.*192A>T		3_prime_UTR_variant	19/19	ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.*192A>T		3_prime_UTR_variant	19/19	2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110731 AN: 151828 Hom.: 40928 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.760 AC: 179624 AN: 236308 Hom.: 69122 Cov.: 4 AF XY: 0.762 AC XY: 92931 AN XY: 122034

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.827

Gnomad4 EAS exome AF: 0.563

Gnomad4 SAS exome AF: 0.839

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.781

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.729 AC: 110810 AN: 151946 Hom.: 40953 Cov.: 32 AF XY: 0.732 AC XY: 54366 AN XY: 74264

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.733

Alfa AF: 0.756 Hom.: 5429

Bravo AF: 0.718

Asia WGS AF: 0.699 AC: 2426 AN: 3472

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.54

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: rs404122; hg19: chr5-39107353; COSMIC: COSV60953134; COSMIC: COSV60953134;