chr3-112928903-G-T

Position:

• chr3-112928903-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138806.4(CD200R1):​c.682C>A​(p.His228Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD200R1 NM_138806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.79

Genes affected

CD200R1 (HGNC:24235): (CD200 receptor 1) This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15194204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1	NM_138806.4	c.682C>A	p.His228Asn	missense_variant	5/8	ENST00000308611.8	NP_620161.1
CD200R1	NM_170780.3	c.613C>A	p.His205Asn	missense_variant	4/7		NP_740750.1
CD200R1	NM_138939.3	c.*240C>A		downstream_gene_variant			NP_620385.1
CD200R1	NM_138940.3	c.*240C>A		downstream_gene_variant			NP_620386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200R1	ENST00000308611.8	c.682C>A	p.His228Asn	missense_variant	5/8	1	NM_138806.4	ENSP00000311035.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.682C>A (p.H228N) alteration is located in exon 5 (coding exon 5) of the CD200R1 gene. This alteration results from a C to A substitution at nucleotide position 682, causing the histidine (H) at amino acid position 228 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.65
DEOGEN2	Benign	0.28	.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.22	.;.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.79	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.15	T;T;T
Vest4		0.15
MutPred		0.48		Gain of ubiquitination at K201 (P = 0.0817);.;.;
MVP		0.28
MPC		0.59
ClinPred		0.58	D
GERP RS		-5.3
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-112647750;