rs6995910

Positions:

• chr8-74033276-G-T

Variant summary

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

The XM_017013299.2(LY96):​c.384+6435G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,926 control chromosomes in the GnomAD database, including 9,310 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 (9310 hom., cov: 31)
• Consequence: LY96 XM_017013299.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY96	XM_017013299.2	c.384+6435G>T		intron_variant			XP_016868788.1
LY96	XM_017013300.2	c.294+6435G>T		intron_variant			XP_016868789.1
		n.74033276G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45392 AN: 151808 Hom.: 9269 Cov.: 31

Gnomad AFR AF: 0.585

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: 0.180

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.299 AC: 45492 AN: 151926 Hom.: 9310 Cov.: 31 AF XY: 0.295 AC XY: 21933 AN XY: 74262

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.284

Alfa AF: 0.257 Hom.: 903

Bravo AF: 0.323

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6995910; hg19: chr8-74945511;