8-74007478-T-C

Variant names:

• chr8-74007478-T-C
• rs10504554
• NM_015364.5:c.203-2523T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015364.5(LY96):​c.203-2523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,178 control chromosomes in the GnomAD database, including 6,992 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 0.26 (6992 hom., cov: 33)
• Consequence: LY96 NM_015364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY96	NM_015364.5	c.203-2523T>C		intron_variant	Intron 2 of 4	ENST00000284818.7	NP_056179.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY96	ENST00000284818.7	c.203-2523T>C		intron_variant	Intron 2 of 4	1	NM_015364.5	ENSP00000284818.2
LY96	ENST00000518893.1	c.113-2523T>C		intron_variant	Intron 1 of 3	3		ENSP00000430533.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39687 AN: 152062 Hom.: 6973 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.261 AC: 39735 AN: 152178 Hom.: 6992 Cov.: 33 AF XY: 0.256 AC XY: 19036 AN XY: 74402

African (AFR) AF: 0.500 AC: 20733 AN: 41462

American (AMR) AF: 0.204 AC: 3116 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.0954 AC: 495 AN: 5186

South Asian (SAS) AF: 0.157 AC: 759 AN: 4832

European-Finnish (FIN) AF: 0.137 AC: 1451 AN: 10594

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11631 AN: 68014

Other (OTH) AF: 0.264 AC: 559 AN: 2116

Alfa AF: 0.206 Hom.: 10704

Bravo AF: 0.279

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		0.84
Mutation Taster		=100/0	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: rs10504554; hg19: chr8-74919713;