4-38779100-T-C

Position:

• chr4-38779100-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030956.4(TLR10):​c.-568-2674A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,156 control chromosomes in the GnomAD database, including 1,706 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 0.11 (1706 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TLR10 NM_030956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.11).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLR10	NM_030956.4	c.-568-2674A>G		intron_variant		ENST00000308973.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLR10	ENST00000308973.9	c.-568-2674A>G		intron_variant		5	NM_030956.4	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16784 AN: 152040 Hom.: 1705 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.113

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.110 AC: 16806 AN: 152156 Hom.: 1706 Cov.: 32 AF XY: 0.110 AC XY: 8191 AN XY: 74396

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0517 Hom.: 622

Bravo AF: 0.125

Asia WGS AF: 0.132 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.30
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs11466612; hg19: chr4-38780721;