chr8-74028651-A-T

Position:

• chr8-74028651-A-T

Variant summary

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

The NM_015364.5(LY96):​c.385-305A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,020 control chromosomes in the GnomAD database, including 9,329 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 0.30 (9329 hom., cov: 32)
• Consequence: LY96 NM_015364.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY96	NM_015364.5	c.385-305A>T		intron_variant		ENST00000284818.7	NP_056179.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY96	ENST00000284818.7	c.385-305A>T		intron_variant		1	NM_015364.5	ENSP00000284818.2
LY96	ENST00000518893.1	c.295-305A>T		intron_variant		3		ENSP00000430533.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45455 AN: 151902 Hom.: 9288 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.300 AC: 45555 AN: 152020 Hom.: 9329 Cov.: 32 AF XY: 0.295 AC XY: 21955 AN XY: 74300

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.283

Alfa AF: 0.257 Hom.: 904

Bravo AF: 0.323

Asia WGS AF: 0.208 AC: 720 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.85

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: rs2114169; hg19: chr8-74940886;