rs2280800

Positions:

• chr6-31678621-C-A

Variant summary

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

The NM_025262.4(LY6G5C):​c.289+480G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,062 control chromosomes in the GnomAD database, including 1,739 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 0.14 (1739 hom., cov: 32)
• Consequence: LY6G5C NM_025262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

Genes affected

LY6G5C (HGNC:13932): (lymphocyte antigen 6 family member G5C) LY6G5C belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G5C	NM_025262.4	c.289+480G>T		intron_variant		ENST00000383237.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY6G5C	ENST00000383237.5	c.289+480G>T		intron_variant		1	NM_025262.4	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20574 AN: 151944 Hom.: 1735 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.135 AC: 20597 AN: 152062 Hom.: 1739 Cov.: 32 AF XY: 0.144 AC XY: 10685 AN XY: 74324

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.105

Alfa AF: 0.127 Hom.: 2206

Bravo AF: 0.125

Asia WGS AF: 0.140 AC: 487 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	7.7
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2280800; hg19: chr6-31646398;