rs11466004

Variant names:

• chr8-74029040-C-A
• NM_015364.5:c.469C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-74029040-C-A
• chr8-74029040-C-G
• chr8-74029040-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015364.5(LY96):​c.469C>A​(p.Pro157Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P157S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LY96 NM_015364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

Genes affected

LY96 (HGNC:17156): (lymphocyte antigen 96) This gene encodes a protein which associates with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccyaride (LPS), thus providing a link between the receptor and LPS signaling. Studies of the mouse ortholog suggest that this gene may be involved in endotoxin neutralization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09287137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY96	NM_015364.5	c.469C>A	p.Pro157Thr	missense_variant	Exon 5 of 5	ENST00000284818.7	NP_056179.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY96	ENST00000284818.7	c.469C>A	p.Pro157Thr	missense_variant	Exon 5 of 5	1	NM_015364.5	ENSP00000284818.2
LY96	ENST00000518893.1	c.379C>A	p.Pro127Thr	missense_variant	Exon 4 of 4	3		ENSP00000430533.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450002 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 722030

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.4
DANN	Benign	0.90
DEOGEN2	Benign	0.33	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.047
Sift	Benign	0.070	T;T
Sift4G	Benign	0.097	T;T
Polyphen		0.26	B;.
Vest4		0.18
MutPred		0.16		Gain of catalytic residue at S159 (P = 0.0857);.;
MVP		0.55
MPC		0.12
ClinPred		0.17	T
GERP RS		3.3
Varity_R		0.31
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-74941275;