chr8-55946443-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002350.4(LYN):​c.133-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,598,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

LYN
NM_002350.4 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00002234
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.140
Variant links:
Genes affected
LYN (HGNC:6735): (LYN proto-oncogene, Src family tyrosine kinase) This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 8-55946443-C-T is Benign according to our data. Variant chr8-55946443-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2899134.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LYNNM_002350.4 linkuse as main transcriptc.133-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000519728.6
LYNNM_001111097.3 linkuse as main transcriptc.70-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
LYNXM_011517529.4 linkuse as main transcriptc.-135-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LYNENST00000519728.6 linkuse as main transcriptc.133-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_002350.4 P4P07948-1
LYNENST00000520220.6 linkuse as main transcriptc.70-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 A1P07948-2
LYNENST00000520050.1 linkuse as main transcriptc.133-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000280
AC:
7
AN:
249866
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135274
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000180
AC:
26
AN:
1446624
Hom.:
0
Cov.:
28
AF XY:
0.0000166
AC XY:
12
AN XY:
720838
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000700
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000127
Gnomad4 OTH exome
AF:
0.0000668
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152118
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 22, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
3.9
DANN
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000022
dbscSNV1_RF
Benign
0.0020
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: rs770738990; hg19: chr8-56859002; API