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4-38773881-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_030956.4(TLR10):c.1710C>T(p.His570=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 1,593,368 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00083 ( 12 hom. )

Consequence

TLR10
NM_030956.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.272
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 Benign. Variant got -11 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=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-38773881-G-A is Benign according to our data. Variant chr4-38773881-G-A is described in ClinVar as [Benign]. Clinvar id is 771360.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=-0.272 with no splicing effect.
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 Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR10NM_030956.4 linkuse as main transcriptc.1710C>T p.His570= synonymous_variant 4/4 ENST00000308973.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR10ENST00000308973.9 linkuse as main transcriptc.1710C>T p.His570= synonymous_variant 4/45 NM_030956.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00113
AC:
172
AN:
152212
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00844
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00635
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00258
AC:
599
AN:
232276
Hom.:
7
AF XY:
0.00207
AC XY:
258
AN XY:
124930
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0163
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00377
Gnomad SAS exome
AF:
0.000115
Gnomad FIN exome
AF:
0.000147
Gnomad NFE exome
AF:
0.0000751
Gnomad OTH exome
AF:
0.000891
GnomAD4 exome
AF:
0.000834
AC:
1202
AN:
1441038
Hom.:
12
Cov.:
35
AF XY:
0.000766
AC XY:
548
AN XY:
715156
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0152
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0118
Gnomad4 SAS exome
AF:
0.0000974
Gnomad4 FIN exome
AF:
0.000209
Gnomad4 NFE exome
AF:
0.0000390
Gnomad4 OTH exome
AF:
0.000638
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00113
AC:
172
AN:
152330
Hom.:
8
Cov.:
32
AF XY:
0.00118
AC XY:
88
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00843
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00636
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000416
Hom.:
1
Bravo
AF:
0.00202
Asia WGS
AF:
0.00462
AC:
16
AN:
3478

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 testingInvitaeJun 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.35
Dann
Benign
0.20

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: rs149045737; hg19: chr4-38775502; COSMIC: COSV58300115; COSMIC: COSV58300115; API