4-38775438-C-T

Variant names:

• chr4-38775438-C-T
• rs10856837
• NM_030956.4:c.153G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_030956.4(TLR10):​c.153G>A​(p.Thr51Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 1,613,984 control chromosomes in the GnomAD database, including 4,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.095 (1193 hom., cov: 32)
  • Exomes 𝑓: 0.048 (3653 hom.)
• Consequence: TLR10 NM_030956.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 15 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.153G>A	p.Thr51Thr	synonymous_variant	Exon 4 of 4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.153G>A	p.Thr51Thr	synonymous_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14484 AN: 152046 Hom.: 1189 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0842 AC: 21137 AN: 251078 AF XY: 0.0827

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.0208

Gnomad NFE exome AF: 0.0337

Gnomad OTH exome AF: 0.0807

GnomAD4 exome AF: 0.0482 AC: 70455 AN: 1461818 Hom.: 3653 Cov.: 35 AF XY: 0.0511 AC XY: 37174 AN XY: 727208

African (AFR) AF: 0.205 AC: 6865 AN: 33480

American (AMR) AF: 0.156 AC: 6968 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2874 AN: 26134

East Asian (EAS) AF: 0.101 AC: 4022 AN: 39692

South Asian (SAS) AF: 0.159 AC: 13674 AN: 86250

European-Finnish (FIN) AF: 0.0232 AC: 1239 AN: 53410

Middle Eastern (MID) AF: 0.121 AC: 696 AN: 5768

European-Non Finnish (NFE) AF: 0.0270 AC: 30022 AN: 1111988

Other (OTH) AF: 0.0678 AC: 4095 AN: 60394

GnomAD4 genome AF: 0.0953 AC: 14508 AN: 152166 Hom.: 1193 Cov.: 32 AF XY: 0.0954 AC XY: 7099 AN XY: 74408

African (AFR) AF: 0.200 AC: 8298 AN: 41474

American (AMR) AF: 0.139 AC: 2124 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3472

East Asian (EAS) AF: 0.0945 AC: 489 AN: 5172

South Asian (SAS) AF: 0.153 AC: 739 AN: 4828

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2050 AN: 68008

Other (OTH) AF: 0.0998 AC: 211 AN: 2114

Alfa AF: 0.0517 Hom.: 1098

Bravo AF: 0.107

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.47
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10856837; hg19: chr4-38777059; COSMIC: COSV58301617; COSMIC: COSV58301617;