4-38775615-T-G

Variant names:

• chr4-38775615-T-G
• rs10856839
• NM_030956.4:c.-25A>C

Variant summary

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

The NM_030956.4(TLR10):​c.-25A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,554,436 control chromosomes in the GnomAD database, including 33,644 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 0.27 (6920 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26724 hom.)
• Consequence: TLR10 NM_030956.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• Publications: 28 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 (AFR) allele frequency at 95% confidence interval = 0.456 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	NM_030956.4	MANE Select	c.-25A>C		5_prime_UTR	Exon 4 of 4	NP_112218.2
	TLR10	NM_001017388.3		c.-25A>C		5_prime_UTR	Exon 2 of 2	NP_001017388.1
	TLR10	NM_001195106.2		c.-25A>C		5_prime_UTR	Exon 3 of 3	NP_001182035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-25A>C		5_prime_UTR	Exon 4 of 4	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.-25A>C		5_prime_UTR	Exon 2 of 2	ENSP00000354459.2
	TLR10	ENST00000506111.1	TSL:1	c.-25A>C		5_prime_UTR	Exon 2 of 2	ENSP00000421483.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41166 AN: 151922 Hom.: 6887 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.238 AC: 49930 AN: 209778 AF XY: 0.239

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.179 AC: 250431 AN: 1402394 Hom.: 26724 Cov.: 29 AF XY: 0.184 AC XY: 127845 AN XY: 692950

African (AFR) AF: 0.477 AC: 14906 AN: 31258

American (AMR) AF: 0.224 AC: 7975 AN: 35548

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5243 AN: 23076

East Asian (EAS) AF: 0.183 AC: 7165 AN: 39156

South Asian (SAS) AF: 0.363 AC: 27367 AN: 75470

European-Finnish (FIN) AF: 0.259 AC: 13357 AN: 51576

Middle Eastern (MID) AF: 0.344 AC: 1890 AN: 5490

European-Non Finnish (NFE) AF: 0.148 AC: 160257 AN: 1083008

Other (OTH) AF: 0.212 AC: 12271 AN: 57812

GnomAD4 genome AF: 0.271 AC: 41246 AN: 152042 Hom.: 6920 Cov.: 32 AF XY: 0.274 AC XY: 20390 AN XY: 74320

African (AFR) AF: 0.461 AC: 19116 AN: 41428

American (AMR) AF: 0.240 AC: 3663 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5180

South Asian (SAS) AF: 0.363 AC: 1751 AN: 4822

European-Finnish (FIN) AF: 0.265 AC: 2804 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11281 AN: 67992

Other (OTH) AF: 0.281 AC: 595 AN: 2116

Alfa AF: 0.218 Hom.: 9046

Bravo AF: 0.271

Asia WGS AF: 0.319 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		-0.10
Mutation Taster		=300/0	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: rs10856839; hg19: chr4-38777236; COSMIC: COSV58299188; COSMIC: COSV58299188;