chr6-111754725-A-G

Position:

• chr6-111754725-A-G

Variant summary

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

The NM_002037.5(FYN):​c.-12+25841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,976 control chromosomes in the GnomAD database, including 26,744 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 0.58 (26744 hom., cov: 30)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FYN NM_002037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYN	NM_002037.5	c.-12+25841T>C		intron_variant		ENST00000354650.7	NP_002028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7	c.-12+25841T>C		intron_variant		1	NM_002037.5	ENSP00000346671	P3

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87415 AN: 151852 Hom.: 26707 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.576 AC: 87511 AN: 151970 Hom.: 26744 Cov.: 30 AF XY: 0.580 AC XY: 43068 AN XY: 74264

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.609

Alfa AF: 0.490 Hom.: 23506

Bravo AF: 0.602

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.45

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: rs6910116; hg19: chr6-112075928; COSMIC: COSV57620877;