rs3730353

Positions:

• chr6-111674463-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.1405+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,572,492 control chromosomes in the GnomAD database, including 18,334 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 0.19 (3528 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14806 hom.)
• Consequence: FYN NM_002037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYN	NM_002037.5	c.1405+36T>C		intron_variant		ENST00000354650.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYN	ENST00000354650.7	c.1405+36T>C		intron_variant		1	NM_002037.5	P3

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28696 AN: 152006 Hom.: 3522 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.142 AC: 33050 AN: 232120 Hom.: 3150 AF XY: 0.135 AC XY: 16957 AN XY: 125648

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.0491

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.133 AC: 189561 AN: 1420368 Hom.: 14806 Cov.: 30 AF XY: 0.131 AC XY: 91877 AN XY: 702926

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.0997

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.0495

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.189 AC: 28725 AN: 152124 Hom.: 3528 Cov.: 32 AF XY: 0.187 AC XY: 13909 AN XY: 74386

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.153

Alfa AF: 0.153 Hom.: 578

Bravo AF: 0.198

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.0
DANN	Benign	0.86

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: rs3730353; hg19: chr6-111995666;