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GeneBe

6-111719926-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002037.5(FYN):c.126C>T(p.Phe42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,614,160 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

FYN
NM_002037.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.680
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-111719926-G-A is Benign according to our data. Variant chr6-111719926-G-A is described in ClinVar as [Benign]. Clinvar id is 709055.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.68 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1735/152270) while in subpopulation AFR AF= 0.0396 (1644/41534). AF 95% confidence interval is 0.038. There are 27 homozygotes in gnomad4. There are 833 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1736 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FYNNM_002037.5 linkuse as main transcriptc.126C>T p.Phe42= synonymous_variant 4/14 ENST00000354650.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FYNENST00000354650.7 linkuse as main transcriptc.126C>T p.Phe42= synonymous_variant 4/141 NM_002037.5 P3P06241-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0114
AC:
1736
AN:
152152
Hom.:
27
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0397
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00438
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00768
GnomAD3 exomes
AF:
0.00285
AC:
717
AN:
251390
Hom.:
17
AF XY:
0.00209
AC XY:
284
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.0387
Gnomad AMR exome
AF:
0.00188
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.00103
AC:
1510
AN:
1461890
Hom.:
25
Cov.:
30
AF XY:
0.000875
AC XY:
636
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0366
Gnomad4 AMR exome
AF:
0.00208
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000396
Gnomad4 OTH exome
AF:
0.00225
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0114
AC:
1735
AN:
152270
Hom.:
27
Cov.:
32
AF XY:
0.0112
AC XY:
833
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0396
Gnomad4 AMR
AF:
0.00438
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00760
Alfa
AF:
0.00580
Hom.:
11
Bravo
AF:
0.0129
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
12
Dann
Benign
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28763978; hg19: chr6-112041129; API