NM_001004303.5:c.953+6289C>T

Variant names:

• chr1-56780886-G-A
• rs1738403
• NM_001004303.5:c.953+6289C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004303.5(FYB2):​c.953+6289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,966 control chromosomes in the GnomAD database, including 17,948 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 0.48 (17948 hom., cov: 32)
• Consequence: FYB2 NM_001004303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB2	NM_001004303.5	c.953+6289C>T		intron_variant	Intron 4 of 19	ENST00000343433.7	NP_001004303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB2	ENST00000343433.7	c.953+6289C>T		intron_variant	Intron 4 of 19	1	NM_001004303.5	ENSP00000345972.6
FYB2	ENST00000484327.1	n.1359+6289C>T		intron_variant	Intron 4 of 13	2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73269 AN: 151848 Hom.: 17930 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.482 AC: 73313 AN: 151966 Hom.: 17948 Cov.: 32 AF XY: 0.483 AC XY: 35853 AN XY: 74252

African (AFR) AF: 0.401 AC: 16644 AN: 41456

American (AMR) AF: 0.498 AC: 7607 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1762 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2303 AN: 5148

South Asian (SAS) AF: 0.427 AC: 2054 AN: 4808

European-Finnish (FIN) AF: 0.609 AC: 6421 AN: 10552

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34957 AN: 67950

Other (OTH) AF: 0.460 AC: 969 AN: 2106

Alfa AF: 0.504 Hom.: 8123

Bravo AF: 0.473

Asia WGS AF: 0.464 AC: 1610 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1738403; hg19: chr1-57246559;