rs453098

Variant names:

• chr6-31723880-G-A
• rs453098
• NM_138272.3:c.303G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138272.3(MPIG6B):​c.303G>A​(p.Gly101Gly) 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
• Publications: 29 publications found

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]

MPIG6B Gene-Disease associations (from GenCC):

• thrombocytopenia, anemia, and myelofibrosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138272.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPIG6B	NM_138272.3	MANE Select	c.303G>A	p.Gly101Gly	synonymous	Exon 2 of 6	NP_612116.1	O95866-1
	MPIG6B	NM_025260.4		c.303G>A	p.Gly101Gly	synonymous	Exon 2 of 6	NP_079536.2
	MPIG6B	NM_138277.3		c.303G>A	p.Gly101Gly	synonymous	Exon 2 of 5	NP_612121.1	O95866-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPIG6B	ENST00000649779.1	MANE Select	c.303G>A	p.Gly101Gly	synonymous	Exon 2 of 6	ENSP00000497720.1	O95866-1
	MPIG6B	ENST00000375809.7	TSL:1	c.303G>A	p.Gly101Gly	synonymous	Exon 2 of 6	ENSP00000364967.3	O95866-2
	MPIG6B	ENST00000375810.8	TSL:1	c.303G>A	p.Gly101Gly	synonymous	Exon 2 of 5	ENSP00000364968.4	O95866-7

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

GnomAD2 exomes AF: 0.0817 AC: 19763 AN: 241770 AF XY: 0.0799

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 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

African (AFR) AF: 0.277 AC: 9218 AN: 33264

American (AMR) AF: 0.0653 AC: 2867 AN: 43878

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 1915 AN: 25836

East Asian (EAS) AF: 0.0217 AC: 860 AN: 39652

South Asian (SAS) AF: 0.0865 AC: 7424 AN: 85826

European-Finnish (FIN) AF: 0.0678 AC: 3602 AN: 53130

Middle Eastern (MID) AF: 0.0992 AC: 569 AN: 5738

European-Non Finnish (NFE) AF: 0.0642 AC: 71242 AN: 1109646

Other (OTH) AF: 0.0760 AC: 4570 AN: 60158

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

African (AFR) AF: 0.267 AC: 11061 AN: 41484

American (AMR) AF: 0.0851 AC: 1301 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 240 AN: 3472

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5178

South Asian (SAS) AF: 0.102 AC: 493 AN: 4824

European-Finnish (FIN) AF: 0.0698 AC: 741 AN: 10614

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4946 AN: 68016

Other (OTH) AF: 0.130 AC: 275 AN: 2110

Alfa AF: 0.0888 Hom.: 2374

Bravo AF: 0.135

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.6
DANN	Benign	0.92
PhyloP100		1.0
PromoterAI		-0.040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs453098; hg19: chr6-31691657;