1-56721687-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004303.5(FYB2):c.1975-1358G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,948 control chromosomes in the GnomAD database, including 7,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7660 hom., cov: 32)
• Consequence: FYB2 NM_001004303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

Genes affected

FYB2 (HGNC:27295): (FYN binding protein 2) Involved in T cell receptor signaling pathway and cell adhesion mediated by integrin. Located in immunological synapse and membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYB2	NM_001004303.5	c.1975-1358G>C		intron_variant		ENST00000343433.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYB2	ENST00000343433.7	c.1975-1358G>C		intron_variant		1	NM_001004303.5	P1
FYB2	ENST00000493000.5	n.892-1358G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46874 AN: 151828 Hom.: 7652 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.324

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46902 AN: 151948 Hom.: 7660 Cov.: 32 AF XY: 0.310 AC XY: 23032 AN XY: 74254

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.334

Alfa AF: 0.171 Hom.: 344

Bravo AF: 0.323

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.81
Dann	Benign	0.44

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: rs1342514; hg19: chr1-57187360;