6-111694367-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002037.5(FYN):c.1273+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00714 in 1,613,986 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (46 hom.)
• Consequence: FYN NM_002037.5 splice_region, intron
• Scores: Splicing: ADA: 0.04223
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.212

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]

LOC105377945 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 6-111694367-G-A is Benign according to our data. Variant chr6-111694367-G-A is described in ClinVar as [Benign]. Clinvar id is 768108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 681 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYN	NM_002037.5	c.1273+8C>T		splice_region_variant, intron_variant		ENST00000354650.7
LOC105377945	XR_001743812.2	n.760G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYN	ENST00000354650.7	c.1273+8C>T		splice_region_variant, intron_variant		1	NM_002037.5	P3

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 681 AN: 152216 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00776

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00558 AC: 1402 AN: 251142 Hom.: 10 AF XY: 0.00604 AC XY: 819 AN XY: 135708

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00700

Gnomad FIN exome AF: 0.00231

Gnomad NFE exome AF: 0.00881

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00742 AC: 10850 AN: 1461652 Hom.: 46 Cov.: 31 AF XY: 0.00734 AC XY: 5335 AN XY: 727106

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00690

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.00859

Gnomad4 OTH exome AF: 0.00633

GnomAD4 genome AF: 0.00446 AC: 680 AN: 152334 Hom.: 1 Cov.: 32 AF XY: 0.00403 AC XY: 300 AN XY: 74486

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.00776

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00625 Hom.: 2

Bravo AF: 0.00433

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00741

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	6.4
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.042
dbscSNV1_RF	Benign	0.14
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: rs3730352; hg19: chr6-112015570; COSMIC: COSV57613922; COSMIC: COSV57613922;