4-38774559-C-A

Variant names:

• chr4-38774559-C-A
• rs11096956
• NM_030956.4:c.1032G>T

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.1032G>T​(p.Pro344Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,591,732 control chromosomes in the GnomAD database, including 42,029 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 0.23 (4585 hom., cov: 33)
  • Exomes 𝑓: 0.21 (37444 hom.)
• Consequence: TLR10 NM_030956.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 41 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=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.1032G>T	p.Pro344Pro	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.1032G>T	p.Pro344Pro	synonymous_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35430 AN: 151990 Hom.: 4580 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.290

GnomAD2 exomes AF: 0.251 AC: 58047 AN: 231240 AF XY: 0.256

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.425

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.212 AC: 305695 AN: 1439624 Hom.: 37444 Cov.: 36 AF XY: 0.218 AC XY: 155565 AN XY: 714946

African (AFR) AF: 0.232 AC: 7477 AN: 32268

American (AMR) AF: 0.267 AC: 10383 AN: 38884

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9373 AN: 25022

East Asian (EAS) AF: 0.490 AC: 19365 AN: 39502

South Asian (SAS) AF: 0.350 AC: 28562 AN: 81558

European-Finnish (FIN) AF: 0.106 AC: 5639 AN: 52974

Middle Eastern (MID) AF: 0.376 AC: 2113 AN: 5626

European-Non Finnish (NFE) AF: 0.190 AC: 209281 AN: 1104362

Other (OTH) AF: 0.227 AC: 13502 AN: 59428

GnomAD4 genome AF: 0.233 AC: 35446 AN: 152108 Hom.: 4585 Cov.: 33 AF XY: 0.231 AC XY: 17178 AN XY: 74356

African (AFR) AF: 0.232 AC: 9620 AN: 41500

American (AMR) AF: 0.307 AC: 4698 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2214 AN: 5184

South Asian (SAS) AF: 0.337 AC: 1626 AN: 4822

European-Finnish (FIN) AF: 0.0964 AC: 1018 AN: 10560

Middle Eastern (MID) AF: 0.348 AC: 101 AN: 290

European-Non Finnish (NFE) AF: 0.206 AC: 13978 AN: 67970

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.232 Hom.: 9921

Bravo AF: 0.250

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-1.0
Mutation Taster		=99/1	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: rs11096956; hg19: chr4-38776180; COSMIC: COSV108163889; COSMIC: COSV108163889;