6-111873293-G-C

Position:

• chr6-111873293-G-C

Variant summary

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

The NM_002037.5(FYN):​c.-448C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 150,128 control chromosomes in the GnomAD database, including 14,865 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 0.39 (14864 hom., cov: 30)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: FYN NM_002037.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYN	NM_002037.5	c.-448C>G		5_prime_UTR_variant	1/14	ENST00000354650.7	NP_002028.1
FYN	XM_047418561.1	c.-407C>G		5_prime_UTR_variant	1/13		XP_047274517.1
FYN	XM_047418569.1	c.-407C>G		5_prime_UTR_variant	1/13		XP_047274525.1
FYN	XM_005266892.5	c.-448C>G		5_prime_UTR_variant	1/13		XP_005266949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7	c.-448C>G		5_prime_UTR_variant	1/14	1	NM_002037.5	ENSP00000346671.3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58203 AN: 149984 Hom.: 14826 Cov.: 30

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.147 AC: 5 AN: 34 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 5 AN XY: 30

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.388 AC: 58286 AN: 150094 Hom.: 14864 Cov.: 30 AF XY: 0.382 AC XY: 28014 AN XY: 73286

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.374

Alfa AF: 0.314 Hom.: 1282

Bravo AF: 0.414

Asia WGS AF: 0.316 AC: 1088 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.4
DANN	Benign	0.58

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: rs1057979; hg19: chr6-112194496;