1-56803848-A-G

Variant names:

• chr1-56803848-A-G
• rs6662617
• NM_001004303.5:c.10-11045T>C

Variant summary

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

The NM_001004303.5(FYB2):​c.10-11045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,054 control chromosomes in the GnomAD database, including 9,767 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 0.34 (9767 hom., cov: 32)
• Consequence: FYB2 NM_001004303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYB2	NM_001004303.5	c.10-11045T>C		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.10-11045T>C		intron_variant	Intron 1 of 19	1	NM_001004303.5	ENSP00000345972.6
FYB2	ENST00000484327.1	n.416-11045T>C		intron_variant	Intron 1 of 13	2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51421 AN: 151936 Hom.: 9768 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.338 AC: 51422 AN: 152054 Hom.: 9767 Cov.: 32 AF XY: 0.332 AC XY: 24648 AN XY: 74306

African (AFR) AF: 0.182 AC: 7538 AN: 41496

American (AMR) AF: 0.285 AC: 4349 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1542 AN: 3472

East Asian (EAS) AF: 0.147 AC: 759 AN: 5180

South Asian (SAS) AF: 0.359 AC: 1730 AN: 4816

European-Finnish (FIN) AF: 0.410 AC: 4324 AN: 10540

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29921 AN: 67962

Other (OTH) AF: 0.339 AC: 716 AN: 2110

Alfa AF: 0.392 Hom.: 25034

Bravo AF: 0.323

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.75
PhyloP100		0.61
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: rs6662617; hg19: chr1-57269521; COSMIC: COSV58583710;