Variant 3-112929487-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138806.4(CD200R1):c.223A>G(p.Lys75Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD200R1
NM_138806.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.696

Variant links:

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]

CD200R1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055532843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1	NM_138806.4 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	4/8	ENST00000308611.8	NP_620161.1	Q8TD46-4
CD200R1	NM_170780.3 linkuse as main transcript	c.154A>G	p.Lys52Glu	missense_variant	3/7		NP_740750.1	Q8TD46-1
CD200R1	NM_138939.3 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	4/4		NP_620385.1	Q8TD46-2
CD200R1	NM_138940.3 linkuse as main transcript	c.154A>G	p.Lys52Glu	missense_variant	3/3		NP_620386.1	Q8TD46-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200R1	ENST00000308611.8 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	4/8	1	NM_138806.4	ENSP00000311035.3		Q8TD46-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247484

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134018

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461062

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.223A>G (p.K75E) alteration is located in exon 4 (coding exon 4) of the CD200R1 gene. This alteration results from a A to G substitution at nucleotide position 223, causing the lysine (K) at amino acid position 75 to be replaced by a glutamic acid (E). 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

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.36

DANN

Benign

0.42

DEOGEN2

Benign

0.0055

.;.;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.42

.;.;T;.;.

M_CAP

Benign

0.0032

MetaRNN

Benign

0.056

T;T;T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.24

N;N;N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.84

T;T;T;T;T

Sift4G

Benign

0.31

T;T;T;T;T

Vest4

0.050

MutPred

0.40

Loss of ubiquitination at K52 (P = 0.0381);.;.;.;Loss of ubiquitination at K52 (P = 0.0381);

MVP

0.11

MPC

0.35

ClinPred

0.021

GERP RS

-2.4

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over