rs453098

Positions:

• chr6-31723880-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138272.3(MPIG6B):​c.303G>A​(p.Gly101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 1,609,320 control chromosomes in the GnomAD database, including 6,497 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 0.13 (1838 hom., cov: 32)
  • Exomes 𝑓: 0.070 (4659 hom.)
• Consequence: MPIG6B NM_138272.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPIG6B	NM_138272.3	c.303G>A	p.Gly101=	synonymous_variant	2/6	ENST00000649779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPIG6B	ENST00000649779.1	c.303G>A	p.Gly101=	synonymous_variant	2/6		NM_138272.3	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19314 AN: 152074 Hom.: 1838 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.0817 AC: 19763 AN: 241770 Hom.: 1204 AF XY: 0.0799 AC XY: 10525 AN XY: 131724

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0609

Gnomad ASJ exome AF: 0.0739

Gnomad EAS exome AF: 0.0356

Gnomad SAS exome AF: 0.0824

Gnomad FIN exome AF: 0.0686

Gnomad NFE exome AF: 0.0718

Gnomad OTH exome AF: 0.0789

GnomAD4 exome AF: 0.0702 AC: 102267 AN: 1457128 Hom.: 4659 Cov.: 34 AF XY: 0.0700 AC XY: 50716 AN XY: 724622

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.0653

Gnomad4 ASJ exome AF: 0.0741

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.0865

Gnomad4 FIN exome AF: 0.0678

Gnomad4 NFE exome AF: 0.0642

Gnomad4 OTH exome AF: 0.0760

GnomAD4 genome AF: 0.127 AC: 19326 AN: 152192 Hom.: 1838 Cov.: 32 AF XY: 0.125 AC XY: 9298 AN XY: 74390

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0851

Gnomad4 ASJ AF: 0.0691

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0840 Hom.: 1044

Bravo AF: 0.135

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.6
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs453098; hg19: chr6-31691657;