Variant 3-112974806-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138806.4(CD200R1):c.52A>G(p.Ile18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,459,600 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CD200R1
NM_138806.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.996

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03789085).

BP6

Variant 3-112974806-T-C is Benign according to our data. Variant chr3-112974806-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2401743.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1	NM_138806.4 linkuse as main transcript	c.52A>G	p.Ile18Val	missense_variant	1/8	ENST00000308611.8	NP_620161.1	Q8TD46-4
CD200R1	NM_170780.3 linkuse as main transcript	c.52A>G	p.Ile18Val	missense_variant	1/7		NP_740750.1	Q8TD46-1
CD200R1	NM_138939.3 linkuse as main transcript	c.52A>G	p.Ile18Val	missense_variant	1/4		NP_620385.1	Q8TD46-2
CD200R1	NM_138940.3 linkuse as main transcript	c.52A>G	p.Ile18Val	missense_variant	1/3		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.52A>G	p.Ile18Val	missense_variant	1/8	1	NM_138806.4	ENSP00000311035.3		Q8TD46-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

250710

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135556

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1459600

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726220

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.19

DANN

Benign

0.19

DEOGEN2

Benign

0.011

.;.;T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.21

.;.;T;.;.

M_CAP

Benign

0.0023

MetaRNN

Benign

0.038

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.050

N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.64

T;T;T;T;T

Sift4G

Benign

0.69

T;T;T;T;T

Vest4

0.028

MutPred

0.23

Gain of catalytic residue at I18 (P = 0.0966);Gain of catalytic residue at I18 (P = 0.0966);Gain of catalytic residue at I18 (P = 0.0966);Gain of catalytic residue at I18 (P = 0.0966);Gain of catalytic residue at I18 (P = 0.0966);

MVP

0.088

MPC

0.21

ClinPred

0.020

GERP RS

-11

gMVP

0.28

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

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