6-111873293-G-C

Variant names:

• chr6-111873293-G-C
• rs1057979
• NM_002037.5:c.-448C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

LOC102724646 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	NM_002037.5	MANE Select	c.-448C>G		5_prime_UTR	Exon 1 of 14	NP_002028.1	P06241-1
	FYN	NM_153047.4		c.-448C>G		upstream_gene	N/A	NP_694592.1	P06241-2
	LOC102724646	NR_168402.1		n.-159G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	ENST00000354650.7	TSL:1 MANE Select	c.-448C>G		5_prime_UTR	Exon 1 of 14	ENSP00000346671.3	P06241-1
	FYN	ENST00000912320.1		c.-448C>G		5_prime_UTR	Exon 1 of 15	ENSP00000582379.1
	FYN	ENST00000966567.1		c.-448C>G		5_prime_UTR	Exon 1 of 15	ENSP00000636626.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.179 AC: 5 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.730 AC: 29839 AN: 40848

American (AMR) AF: 0.317 AC: 4809 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1048 AN: 3452

East Asian (EAS) AF: 0.363 AC: 1793 AN: 4940

South Asian (SAS) AF: 0.341 AC: 1631 AN: 4784

European-Finnish (FIN) AF: 0.161 AC: 1665 AN: 10314

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16427 AN: 67282

Other (OTH) AF: 0.374 AC: 781 AN: 2090

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.4
DANN	Benign	0.58
PhyloP100		0.055
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	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: rs1057979; hg19: chr6-112194496;