rs15574

Positions:

• chr6-31718720-G-A
• chr6-31718720-G-C

Variant summary

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

The NM_025261.3(LY6G6C):​c.*376C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 291,228 control chromosomes in the GnomAD database, including 13,210 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 0.32 (8723 hom., cov: 30)
  • Exomes 𝑓: 0.24 (4487 hom.)
• Consequence: LY6G6C NM_025261.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

Genes affected

LY6G6C (HGNC:13936): (lymphocyte antigen 6 family member G6C) LY6G6C 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]

MPIG6B (HGNC:13937): (megakaryocyte and platelet inhibitory receptor G6b) This gene is a member of the immunoglobulin (Ig) superfamily and is located in the major histocompatibility complex (MHC) class III region. The protein encoded by this gene is a glycosylated, plasma membrane-bound cell surface receptor, but soluble isoforms encoded by some transcript variants have been found in the endoplasmic reticulum and Golgi before being secreted. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G6C	NM_025261.3	c.*376C>T		3_prime_UTR_variant	3/3	ENST00000375819.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY6G6C	ENST00000375819.3	c.*376C>T		3_prime_UTR_variant	3/3	1	NM_025261.3	P1
LY6G6C	ENST00000495859.1	c.*376C>T		3_prime_UTR_variant	4/4	1
MPIG6B	ENST00000460663.5	n.90+37G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48461 AN: 151686 Hom.: 8704 Cov.: 30

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.236 AC: 32899 AN: 139424 Hom.: 4487 Cov.: 0 AF XY: 0.233 AC XY: 16257 AN XY: 69910

Gnomad4 AFR exome AF: 0.443

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.320 AC: 48533 AN: 151804 Hom.: 8723 Cov.: 30 AF XY: 0.326 AC XY: 24223 AN XY: 74194

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.319

Alfa AF: 0.218 Hom.: 4187

Bravo AF: 0.324

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.62

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: rs15574; hg19: chr6-31686497;