4-38775850-C-T

Variant names:

• chr4-38775850-C-T
• rs4274855
• NM_030956.4:c.-138G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030956.4(TLR10):​c.-138G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 316,004 control chromosomes in the GnomAD database, including 5,639 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 0.14 (1957 hom., cov: 32)
  • Exomes 𝑓: 0.20 (3682 hom.)
• Consequence: TLR10 NM_030956.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 31 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030956.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.-138G>A		5_prime_UTR	Exon 3 of 4	NP_112218.2	Q9BXR5
	TLR10	NM_001195107.2		c.-138G>A		5_prime_UTR	Exon 2 of 3	NP_001182036.1	Q9BXR5
	TLR10	NM_001017388.3		c.-62-198G>A		intron	N/A	NP_001017388.1	Q9BXR5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-138G>A		5_prime_UTR	Exon 3 of 4	ENSP00000308925.4	Q9BXR5
	TLR10	ENST00000506111.1	TSL:1	c.-138G>A		5_prime_UTR	Exon 1 of 2	ENSP00000421483.1	Q9BXR5
	TLR10	ENST00000361424.6	TSL:1	c.-62-198G>A		intron	N/A	ENSP00000354459.2	Q9BXR5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20908 AN: 151992 Hom.: 1957 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.195 AC: 31961 AN: 163894 Hom.: 3682 Cov.: 2 AF XY: 0.196 AC XY: 16678 AN XY: 85282

African (AFR) AF: 0.0393 AC: 188 AN: 4780

American (AMR) AF: 0.154 AC: 1110 AN: 7224

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 1658 AN: 6042

East Asian (EAS) AF: 0.433 AC: 5836 AN: 13486

South Asian (SAS) AF: 0.184 AC: 1275 AN: 6934

European-Finnish (FIN) AF: 0.0887 AC: 671 AN: 7566

Middle Eastern (MID) AF: 0.270 AC: 215 AN: 796

European-Non Finnish (NFE) AF: 0.179 AC: 19144 AN: 106688

Other (OTH) AF: 0.180 AC: 1864 AN: 10378

GnomAD4 genome AF: 0.137 AC: 20900 AN: 152110 Hom.: 1957 Cov.: 32 AF XY: 0.135 AC XY: 10061 AN XY: 74354

African (AFR) AF: 0.0315 AC: 1308 AN: 41498

American (AMR) AF: 0.168 AC: 2569 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 956 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1717 AN: 5166

South Asian (SAS) AF: 0.182 AC: 878 AN: 4816

European-Finnish (FIN) AF: 0.0785 AC: 831 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11924 AN: 67982

Other (OTH) AF: 0.186 AC: 393 AN: 2110

Alfa AF: 0.181 Hom.: 3601

Bravo AF: 0.143

Asia WGS AF: 0.186 AC: 648 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.57
PhyloP100		0.11
PromoterAI		-0.038	Neutral
Mutation Taster		=297/3	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: rs4274855; hg19: chr4-38777471;