rs10489622

Variant names:

• chr1-56809980-T-C
• rs10489622
• NM_001004303.5:c.9+9302A>G

Variant summary

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

The NM_001004303.5(FYB2):​c.9+9302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 151,900 control chromosomes in the GnomAD database, including 573 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 0.075 (573 hom., cov: 32)
• Consequence: FYB2 NM_001004303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.955
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB2	NM_001004303.5	c.9+9302A>G		intron_variant	Intron 1 of 19	ENST00000343433.7	NP_001004303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYB2	ENST00000343433.7	c.9+9302A>G		intron_variant	Intron 1 of 19	1	NM_001004303.5	ENSP00000345972.6
FYB2	ENST00000484327.1	n.415+9302A>G		intron_variant	Intron 1 of 13	2

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11442 AN: 151780 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0754 AC: 11448 AN: 151900 Hom.: 573 Cov.: 32 AF XY: 0.0761 AC XY: 5649 AN XY: 74246

African (AFR) AF: 0.0190 AC: 786 AN: 41410

American (AMR) AF: 0.101 AC: 1539 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3464

East Asian (EAS) AF: 0.0920 AC: 475 AN: 5164

South Asian (SAS) AF: 0.137 AC: 658 AN: 4808

European-Finnish (FIN) AF: 0.0787 AC: 829 AN: 10536

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0963 AC: 6544 AN: 67944

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.0783 Hom.: 308

Bravo AF: 0.0740

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.6
DANN	Benign	0.47
PhyloP100		0.95
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: rs10489622; hg19: chr1-57275653;