6-111694538-C-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.1120-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,614,110 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (119 hom.)
• Consequence: FYN NM_002037.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002159
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.155

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=-0.73).
• BP6: Variant 6-111694538-C-T is Benign according to our data. Variant chr6-111694538-C-T is described in ClinVar as [Benign]. Clinvar id is 770554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYN	NM_002037.5	c.1120-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000354650.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYN	ENST00000354650.7	c.1120-10G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002037.5	P3

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3590 AN: 152168 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0808

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: 0.000794

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00657 AC: 1652 AN: 251294 Hom.: 58 AF XY: 0.00477 AC XY: 648 AN XY: 135796

Gnomad AFR exome AF: 0.0826

Gnomad AMR exome AF: 0.00573

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00270 AC: 3947 AN: 1461824 Hom.: 119 Cov.: 32 AF XY: 0.00238 AC XY: 1728 AN XY: 727204

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.00593

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000403

Gnomad4 OTH exome AF: 0.00621

GnomAD4 genome AF: 0.0238 AC: 3627 AN: 152286 Hom.: 167 Cov.: 32 AF XY: 0.0237 AC XY: 1763 AN XY: 74468

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0197 Hom.: 38

Bravo AF: 0.0265

Asia WGS AF: 0.0120 AC: 40 AN: 3478

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	5.2
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.028
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: rs804187; hg19: chr6-112015741;