rs5744079

Variant names:

• chrX-12919601-C-T
• rs5744079
• NM_138636.5:c.561C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-12919601-C-T
• chrX-12919601-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_138636.5(TLR8):​c.561C>T​(p.Cys187Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,206,965 control chromosomes in the GnomAD database, including 40 homozygotes. There are 723 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (15 hom., 353 hem., cov: 23)
  • Exomes 𝑓: 0.0013 (25 hom. 370 hem.)
• Consequence: TLR8 NM_138636.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.521
• Publications: 2 publications found

Genes affected

TLR8 (HGNC:15632): (toll like receptor 8) 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 predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008]

TLR8-AS1 (HGNC:40720): (TLR8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-12919601-C-T is Benign according to our data. Variant chrX-12919601-C-T is described in ClinVar as Benign. ClinVar VariationId is 784429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.521 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1309/111805) while in subpopulation AFR AF = 0.0402 (1238/30773). AF 95% confidence interval is 0.0384. There are 15 homozygotes in GnomAd4. There are 353 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138636.5. 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
	TLR8	NM_138636.5	MANE Select	c.561C>T	p.Cys187Cys	synonymous	Exon 2 of 2	NP_619542.1	Q9NR97-1
	TLR8	NM_016610.4		c.615C>T	p.Cys205Cys	synonymous	Exon 3 of 3	NP_057694.2
	TLR8-AS1	NR_030727.1		n.241-11268G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLR8	ENST00000218032.7	TSL:1 MANE Select	c.561C>T	p.Cys187Cys	synonymous	Exon 2 of 2	ENSP00000218032.7	Q9NR97-1
	TLR8	ENST00000311912.5	TSL:1	c.615C>T	p.Cys205Cys	synonymous	Exon 3 of 3	ENSP00000312082.5	Q9NR97-2

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1309 AN: 111754 Hom.: 15 Cov.: 23

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00494

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000369

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.00354 AC: 630 AN: 178165 AF XY: 0.00248

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000747

Gnomad OTH exome AF: 0.00251

GnomAD4 exome AF: 0.00132 AC: 1445 AN: 1095160 Hom.: 25 Cov.: 32 AF XY: 0.00103 AC XY: 370 AN XY: 360958

African (AFR) AF: 0.0424 AC: 1114 AN: 26273

American (AMR) AF: 0.00314 AC: 109 AN: 34676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19264

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30182

South Asian (SAS) AF: 0.000619 AC: 33 AN: 53285

European-Finnish (FIN) AF: 0.0000494 AC: 2 AN: 40497

Middle Eastern (MID) AF: 0.000973 AC: 4 AN: 4113

European-Non Finnish (NFE) AF: 0.0000523 AC: 44 AN: 840867

Other (OTH) AF: 0.00300 AC: 138 AN: 46003

GnomAD4 genome AF: 0.0117 AC: 1309 AN: 111805 Hom.: 15 Cov.: 23 AF XY: 0.0104 AC XY: 353 AN XY: 34031

African (AFR) AF: 0.0402 AC: 1238 AN: 30773

American (AMR) AF: 0.00494 AC: 52 AN: 10529

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3575

South Asian (SAS) AF: 0.000371 AC: 1 AN: 2698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6015

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53142

Other (OTH) AF: 0.0105 AC: 16 AN: 1529

Alfa AF: 0.00560 Hom.: 11

Bravo AF: 0.0138

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.53
DANN	Benign	0.43
PhyloP100		-0.52
Mutation Taster		=98/2	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: rs5744079; hg19: chrX-12937720;