Variant 3-112819833-G-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_001199215.3(CD200R1L):c.679C>G(p.Leu227Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,610,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CD200R1L
NM_001199215.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.486

Variant links:

Genes affected

CD200R1L (HGNC:24665): (CD200 receptor 1 like) Predicted to enable signaling receptor activity. Predicted to be involved in regulation of neuroinflammatory response. Predicted to be integral component of membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CD200R1L links:

CD200R1L-AS1 (HGNC:):

CD200R1L-AS1 links:

Genome browser will be placed here

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=0.0534198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1L	NM_001199215.3 linkuse as main transcript	c.679C>G	p.Leu227Val	missense_variant	7/8	ENST00000488794.6	NP_001186144.1	Q6Q8B3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD200R1L	ENST00000488794.6 linkuse as main transcript	c.679C>G	p.Leu227Val	missense_variant	7/8	5	NM_001199215.3	ENSP00000418413.1	Q6Q8B3-2
CD200R1L	ENST00000398214.5 linkuse as main transcript	c.742C>G	p.Leu248Val	missense_variant	5/6	1		ENSP00000381272.1	Q6Q8B3-1
CD200R1L	ENST00000486723.1 linkuse as main transcript	n.*741C>G		non_coding_transcript_exon_variant	7/8	2		ENSP00000420461.1	F8WDF0
CD200R1L	ENST00000486723.1 linkuse as main transcript	n.*741C>G		3_prime_UTR_variant	7/8	2		ENSP00000420461.1	F8WDF0

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

246132

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000339

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458706

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

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

AF:

0.00000658

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000331

AC:

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

Nov 06, 2023

The c.742C>G (p.L248V) alteration is located in exon 5 (coding exon 5) of the CD200R1L gene. This alteration results from a C to G substitution at nucleotide position 742, causing the leucine (L) at amino acid position 248 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.87

DANN

Benign

0.95

DEOGEN2

Benign

0.012

T;.;.;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.49

T;T;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

N;N;N;.

REVEL

Benign

0.031

Sift

Benign

0.097

T;T;T;.

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.58

P;.;.;.

Vest4

0.17

MutPred

0.34

Gain of methylation at K245 (P = 0.0627);.;.;.;

MVP

0.18

MPC

0.19

ClinPred

0.12

GERP RS

-0.99

Varity_R

0.063

gMVP

0.24

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