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4-38774085-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_030956.4(TLR10):c.1506C>T(p.Ser502=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,612,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 0 hom. )

Consequence

TLR10
NM_030956.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.704
Variant links:
Genes affected
TLR10 (HGNC:15634): (toll like receptor 10) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is most highly expressed in lymphoid tissues such as spleen, lymph node, thymus, and tonsil. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-38774085-G-A is Benign according to our data. Variant chr4-38774085-G-A is described in ClinVar as [Benign]. Clinvar id is 719669.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=-0.704 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR10NM_030956.4 linkuse as main transcriptc.1506C>T p.Ser502= synonymous_variant 4/4 ENST00000308973.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR10ENST00000308973.9 linkuse as main transcriptc.1506C>T p.Ser502= synonymous_variant 4/45 NM_030956.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00124
AC:
189
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.00334
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00144
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00127
AC:
318
AN:
249754
Hom.:
0
AF XY:
0.00120
AC XY:
163
AN XY:
135336
show subpopulations
Gnomad AFR exome
AF:
0.000574
Gnomad AMR exome
AF:
0.00250
Gnomad ASJ exome
AF:
0.00189
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00171
Gnomad OTH exome
AF:
0.00116
GnomAD4 exome
AF:
0.00123
AC:
1802
AN:
1460174
Hom.:
0
Cov.:
35
AF XY:
0.00125
AC XY:
908
AN XY:
726020
show subpopulations
Gnomad4 AFR exome
AF:
0.000658
Gnomad4 AMR exome
AF:
0.00253
Gnomad4 ASJ exome
AF:
0.00165
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000209
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00136
Gnomad4 OTH exome
AF:
0.00124
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00124
AC:
189
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.00113
AC XY:
84
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.000505
Gnomad4 AMR
AF:
0.00333
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00144
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00131
Hom.:
0
Bravo
AF:
0.00176
EpiCase
AF:
0.00185
EpiControl
AF:
0.00219

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 testingInvitaeJul 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
6.1
Dann
Benign
0.50

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: rs41305286; hg19: chr4-38775706; COSMIC: COSV100458143; COSMIC: COSV100458143; API