rs1050572

Positions:

• chr3-112347715-G-A

Variant summary

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

The NM_005944.7(CD200):​c.579G>A​(p.Thr193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,630 control chromosomes in the GnomAD database, including 12,039 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 0.15 (2362 hom., cov: 32)
  • Exomes 𝑓: 0.098 (9677 hom.)
• Consequence: CD200 NM_005944.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

Genes affected

CD200 (HGNC:7203): (CD200 molecule) This gene encodes a type I membrane glycoprotein containing two extracellular immunoglobulin domains, a transmembrane and a cytoplasmic domain. This gene is expressed by various cell types, including B cells, a subset of T cells, thymocytes, endothelial cells, and neurons. The encoded protein plays an important role in immunosuppression and regulation of anti-tumor activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-1.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200	NM_005944.7	c.579G>A	p.Thr193=	synonymous_variant	4/6	ENST00000315711.12	NP_005935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200	ENST00000315711.12	c.579G>A	p.Thr193=	synonymous_variant	4/6	1	NM_005944.7	ENSP00000312766	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22600 AN: 151842 Hom.: 2342 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.128 AC: 32094 AN: 251358 Hom.: 2970 AF XY: 0.131 AC XY: 17848 AN XY: 135834

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.0610

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.0965

Gnomad NFE exome AF: 0.0793

Gnomad OTH exome AF: 0.0984

GnomAD4 exome AF: 0.0978 AC: 142881 AN: 1461672 Hom.: 9677 Cov.: 33 AF XY: 0.102 AC XY: 74047 AN XY: 727144

Gnomad4 AFR exome AF: 0.302

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.0602

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0760

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.149 AC: 22662 AN: 151958 Hom.: 2362 Cov.: 32 AF XY: 0.152 AC XY: 11255 AN XY: 74264

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0926 Hom.: 2049

Bravo AF: 0.153

Asia WGS AF: 0.282 AC: 980 AN: 3478

EpiCase AF: 0.0765

EpiControl AF: 0.0837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.058
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1050572; hg19: chr3-112066562; COSMIC: COSV59862537; COSMIC: COSV59862537;