5-39110312-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001465.6(FYB1):c.2435+44T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,333,202 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (124 hom.)
• Consequence: FYB1 NM_001465.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129

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=-0.8).
• BP6: Variant 5-39110312-A-T is Benign according to our data. Variant chr5-39110312-A-T is described in ClinVar as [Benign]. Clinvar id is 1256832.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0182 (2764/152170) while in subpopulation EAS AF= 0.0513 (266/5186). AF 95% confidence interval is 0.0493. There are 51 homozygotes in gnomad4. There are 1381 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB1	NM_001465.6	c.2435+44T>A		intron_variant		ENST00000512982.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB1	ENST00000512982.4	c.2435+44T>A		intron_variant		2	NM_001465.6	P4

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2763 AN: 152052 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00656

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.00801

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.0108 AC: 2312 AN: 214904 Hom.: 48 AF XY: 0.00981 AC XY: 1151 AN XY: 117288

Gnomad AFR exome AF: 0.0514

Gnomad AMR exome AF: 0.00343

Gnomad ASJ exome AF: 0.00269

Gnomad EAS exome AF: 0.0476

Gnomad SAS exome AF: 0.0166

Gnomad FIN exome AF: 0.00929

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00930

GnomAD4 exome AF: 0.00481 AC: 5684 AN: 1181032 Hom.: 124 Cov.: 16 AF XY: 0.00496 AC XY: 2960 AN XY: 596512

Gnomad4 AFR exome AF: 0.0520

Gnomad4 AMR exome AF: 0.00392

Gnomad4 ASJ exome AF: 0.00306

Gnomad4 EAS exome AF: 0.0482

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.00837

Gnomad4 NFE exome AF: 0.000373

Gnomad4 OTH exome AF: 0.00862

GnomAD4 genome AF: 0.0182 AC: 2764 AN: 152170 Hom.: 51 Cov.: 32 AF XY: 0.0186 AC XY: 1381 AN XY: 74400

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.00656

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.0190

Gnomad4 FIN AF: 0.00801

Gnomad4 NFE AF: 0.000868

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00916 Hom.: 5

Bravo AF: 0.0196

Asia WGS AF: 0.0350 AC: 120 AN: 3474

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 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.1
Dann	Benign	0.78

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: rs77289629; hg19: chr5-39110414; COSMIC: COSV60949704;