6-111694620-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002037.5(FYN):c.1119+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,613,946 control chromosomes in the GnomAD database, including 250 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 0.023 (150 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (100 hom.)
• Consequence: FYN NM_002037.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003504
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-111694620-G-T is Benign according to our data. Variant chr6-111694620-G-T is described in ClinVar as [Benign]. Clinvar id is 770555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYN	NM_002037.5	c.1119+8C>A		splice_region_variant, intron_variant		ENST00000354650.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYN	ENST00000354650.7	c.1119+8C>A		splice_region_variant, intron_variant		1	NM_002037.5	P3

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3433 AN: 152152 Hom.: 143 Cov.: 33

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00617 AC: 1551 AN: 251232 Hom.: 47 AF XY: 0.00444 AC XY: 603 AN XY: 135770

Gnomad AFR exome AF: 0.0780

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000572

Gnomad OTH exome AF: 0.00343

GnomAD4 exome AF: 0.00258 AC: 3766 AN: 1461676 Hom.: 100 Cov.: 31 AF XY: 0.00227 AC XY: 1647 AN XY: 727138

Gnomad4 AFR exome AF: 0.0782

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000396

Gnomad4 OTH exome AF: 0.00585

GnomAD4 genome AF: 0.0228 AC: 3465 AN: 152270 Hom.: 150 Cov.: 33 AF XY: 0.0224 AC XY: 1671 AN XY: 74452

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00523 Hom.: 26

Bravo AF: 0.0253

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00107

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

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000035
dbscSNV1_RF	Benign	0.0
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: rs804186; hg19: chr6-112015823;