8-74007478-T-C

Position:

• chr8-74007478-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.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

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=-0.89).
• 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/exons	MANE	Protein	UniProt
LY96	NM_015364.5	c.203-2523T>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.203-2523T>C		intron_variant		1	NM_015364.5	ENSP00000284818	P1
LY96	ENST00000518893.1	c.113-2523T>C		intron_variant		3		ENSP00000430533

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

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0954

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.264

Alfa AF: 0.192 Hom.: 3552

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

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: rs10504554; hg19: chr8-74919713;