rs16938755

Positions:

• chr8-73991901-T-C

Variant summary

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

The NM_015364.5(LY96):​c.112+347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,076 control chromosomes in the GnomAD database, including 3,284 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 0.19 (3284 hom., cov: 32)
• Consequence: LY96 NM_015364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

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 (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY96	NM_015364.5	c.112+347T>C		intron_variant		ENST00000284818.7	NP_056179.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY96	ENST00000284818.7	c.112+347T>C		intron_variant		1	NM_015364.5	ENSP00000284818	P1
LY96	ENST00000518893.1	c.112+347T>C		intron_variant		3		ENSP00000430533

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28514 AN: 151956 Hom.: 3274 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.188 AC: 28547 AN: 152076 Hom.: 3284 Cov.: 32 AF XY: 0.185 AC XY: 13724 AN XY: 74382

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0968

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.201

Alfa AF: 0.167 Hom.: 333

Bravo AF: 0.199

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs16938755; hg19: chr8-74904136;