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GeneBe

4-38774483-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_030956.4(TLR10):c.1108C>T(p.Gln370Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,598,288 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 12 hom. )

Consequence

TLR10
NM_030956.4 stop_gained

Scores

1
3
3

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.758
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 -8 ACMG points.

PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Stoplost variant in NM_030956.4 Downstream stopcodon found after 831 codons.
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-38774483-G-A is Benign according to our data. Variant chr4-38774483-G-A is described in ClinVar as [Benign]. Clinvar id is 775957.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00633 (964/152282) while in subpopulation AFR AF= 0.022 (914/41546). AF 95% confidence interval is 0.0208. There are 13 homozygotes in gnomad4. There are 448 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 Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TLR10NM_030956.4 linkuse as main transcriptc.1108C>T p.Gln370Ter stop_gained 4/4 ENST00000308973.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TLR10ENST00000308973.9 linkuse as main transcriptc.1108C>T p.Gln370Ter stop_gained 4/45 NM_030956.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00632
AC:
961
AN:
152164
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0220
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
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:
0.000103
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00155
AC:
364
AN:
234894
Hom.:
3
AF XY:
0.00113
AC XY:
143
AN XY:
126866
show subpopulations
Gnomad AFR exome
AF:
0.0208
Gnomad AMR exome
AF:
0.000697
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000376
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000367
Gnomad OTH exome
AF:
0.000876
GnomAD4 exome
AF:
0.000576
AC:
833
AN:
1446006
Hom.:
12
Cov.:
35
AF XY:
0.000495
AC XY:
356
AN XY:
718614
show subpopulations
Gnomad4 AFR exome
AF:
0.0209
Gnomad4 AMR exome
AF:
0.00105
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000121
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000172
Gnomad4 OTH exome
AF:
0.00152
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00633
AC:
964
AN:
152282
Hom.:
13
Cov.:
32
AF XY:
0.00602
AC XY:
448
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0220
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00123
Hom.:
3
Bravo
AF:
0.00736
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0168
AC:
74
ESP6500EA
AF:
0.000116
AC:
1
ExAC
?
    Exome Aggregation Consortium database
AF:
0.00183
AC:
222
Asia WGS
AF:
0.00202
AC:
7
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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.035
T
BayesDel_noAF
Pathogenic
0.29
Cadd
Pathogenic
37
Dann
Uncertain
1.0
Eigen
Uncertain
0.27
Eigen_PC
Benign
-0.0070
FATHMM_MKL
Benign
0.27
N
MutationTaster
Benign
1.0
D;D;D;D
Vest4
0.74
GERP RS
3.3

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: rs62617795; hg19: chr4-38776104; COSMIC: COSV99058001; COSMIC: COSV99058001; API