8-74029040-C-T

Variant names:

• chr8-74029040-C-T
• rs11466004
• NM_015364.5:c.469C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015364.5(LY96):​c.469C>T​(p.Pro157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,601,498 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.016 (223 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031943023).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0126 (1918/152102) while in subpopulation NFE AF= 0.0178 (1213/68010). AF 95% confidence interval is 0.017. There are 21 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY96	NM_015364.5	c.469C>T	p.Pro157Ser	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>T	p.Pro157Ser	missense_variant	Exon 5 of 5	1	NM_015364.5	ENSP00000284818.2
LY96	ENST00000518893.1	c.379C>T	p.Pro127Ser	missense_variant	Exon 4 of 4	3		ENSP00000430533.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1919 AN: 151984 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00312

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00686

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.0129 AC: 3231 AN: 250124 Hom.: 29 AF XY: 0.0133 AC XY: 1793 AN XY: 135246

Gnomad AFR exome AF: 0.00334

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00786

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00684

Gnomad FIN exome AF: 0.0198

Gnomad NFE exome AF: 0.0168

Gnomad OTH exome AF: 0.0195

GnomAD4 exome AF: 0.0161 AC: 23381 AN: 1449396 Hom.: 223 Cov.: 27 AF XY: 0.0160 AC XY: 11518 AN XY: 721756

Gnomad4 AFR exome AF: 0.00274

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.00783

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00761

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0180

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0126 AC: 1918 AN: 152102 Hom.: 21 Cov.: 32 AF XY: 0.0124 AC XY: 923 AN XY: 74368

Gnomad4 AFR AF: 0.00311

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00666

Gnomad4 FIN AF: 0.0188

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0146 Hom.: 27

Bravo AF: 0.0125

TwinsUK AF: 0.0191 AC: 71

ALSPAC AF: 0.0148 AC: 57

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0198 AC: 170

ExAC AF: 0.0128 AC: 1551

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0172

EpiControl AF: 0.0183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.0
DANN	Benign	0.66
DEOGEN2	Benign	0.32	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0032	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Benign	0.057
Sift	Benign	0.17	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.021	B;.
Vest4		0.058
MPC		0.11
ClinPred		0.0051	T
GERP RS		3.3
Varity_R		0.22
gMVP		0.73

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: rs11466004; hg19: chr8-74941275;