chr3-112929328-T-G

Position:

• chr3-112929328-T-G

Variant summary

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

The NM_138806.4(CD200R1):​c.382A>C​(p.Ile128Leu) 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. 12/18 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: 0.264

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=0.16515708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1	NM_138806.4	c.382A>C	p.Ile128Leu	missense_variant	4/8	ENST00000308611.8	NP_620161.1
CD200R1	NM_170780.3	c.313A>C	p.Ile105Leu	missense_variant	3/7		NP_740750.1
CD200R1	NM_138939.3	c.382A>C	p.Ile128Leu	missense_variant	4/4		NP_620385.1
CD200R1	NM_138940.3	c.313A>C	p.Ile105Leu	missense_variant	3/3		NP_620386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200R1	ENST00000308611.8	c.382A>C	p.Ile128Leu	missense_variant	4/8	1	NM_138806.4	ENSP00000311035.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 77

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

Aug 04, 2023

The c.382A>C (p.I128L) alteration is located in exon 4 (coding exon 4) of the CD200R1 gene. This alteration results from a A to C substitution at nucleotide position 382, causing the isoleucine (I) at amino acid position 128 to be replaced by a leucine (L). 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	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	.;.;T;.;.
Eigen	Benign	-0.066
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.78	.;.;T;.;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.074
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Benign	0.15	T;T;T;D;D
Vest4		0.19
MutPred		0.51		Gain of catalytic residue at I105 (P = 0.0435);.;.;.;Gain of catalytic residue at I105 (P = 0.0435);
MVP		0.17
MPC		0.89
ClinPred		0.80	D
GERP RS		2.9
gMVP		0.34

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: chr3-112648175;