4-38778850-T-C

Variant names:

• chr4-38778850-T-C
• rs11466617
• NM_030956.4:c.-568-2424A>G

Variant summary

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

The NM_030956.4(TLR10):​c.-568-2424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,244 control chromosomes in the GnomAD database, including 1,963 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 (1962 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 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.-568-2424A>G		intron	N/A	NP_112218.2
	TLR10	NM_001017388.3		c.-62-3198A>G		intron	N/A	NP_001017388.1
	TLR10	NM_001195106.2		c.-379-2424A>G		intron	N/A	NP_001182035.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR10	ENST00000308973.9	TSL:5 MANE Select	c.-568-2424A>G		intron	N/A	ENSP00000308925.4
	TLR10	ENST00000361424.6	TSL:1	c.-62-3198A>G		intron	N/A	ENSP00000354459.2
	TLR10	ENST00000613579.4	TSL:3	c.-379-2424A>G		intron	N/A	ENSP00000478206.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20931 AN: 152104 Hom.: 1962 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.182 AC: 4 AN: 22 Hom.: 1 AF XY: 0.182 AC XY: 4 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 2 AN: 18

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.137 AC: 20923 AN: 152222 Hom.: 1962 Cov.: 32 AF XY: 0.135 AC XY: 10077 AN XY: 74426

African (AFR) AF: 0.0317 AC: 1316 AN: 41570

American (AMR) AF: 0.168 AC: 2566 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5170

South Asian (SAS) AF: 0.183 AC: 882 AN: 4814

European-Finnish (FIN) AF: 0.0780 AC: 827 AN: 10598

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

European-Non Finnish (NFE) AF: 0.175 AC: 11932 AN: 67996

Other (OTH) AF: 0.186 AC: 394 AN: 2114

Alfa AF: 0.128 Hom.: 254

Bravo AF: 0.143

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.69
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: rs11466617; hg19: chr4-38780471;