Variant 3-112827188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001199215.3(CD200R1L):c.421G>A(p.Ala141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CD200R1L
NM_001199215.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1L	NM_001199215.3 linkuse as main transcript	c.421G>A	p.Ala141Thr	missense_variant	6/8	ENST00000488794.6	NP_001186144.1	Q6Q8B3-2
CD200R1L	NM_001008784.4 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	5/7		NP_001008784.2	Q6Q8B3-1
CD200R1L	NM_001370552.3 linkuse as main transcript	c.421G>A	p.Ala141Thr	missense_variant	7/9		NP_001357481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD200R1L	ENST00000488794.6 linkuse as main transcript	c.421G>A	p.Ala141Thr	missense_variant	6/8	5	NM_001199215.3	ENSP00000418413.1	Q6Q8B3-2
CD200R1L	ENST00000398214.5 linkuse as main transcript	c.484G>A	p.Ala162Thr	missense_variant	4/6	1		ENSP00000381272.1	Q6Q8B3-1
CD200R1L	ENST00000486723.1 linkuse as main transcript	n.*483G>A		non_coding_transcript_exon_variant	6/8	2		ENSP00000420461.1	F8WDF0
CD200R1L	ENST00000486723.1 linkuse as main transcript	n.*483G>A		3_prime_UTR_variant	6/8	2		ENSP00000420461.1	F8WDF0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

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:

0.0000120

AC:

AN:

250350

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461300

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

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:

0.0000165

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 10, 2023

The c.484G>A (p.A162T) alteration is located in exon 4 (coding exon 4) of the CD200R1L gene. This alteration results from a G to A substitution at nucleotide position 484, causing the alanine (A) at amino acid position 162 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

D;.;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.93

D;D;D;D

MetaSVM

Uncertain

0.36

MutationAssessor

Uncertain

2.7

M;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.5

D;D;D;.

REVEL

Uncertain

0.53

Sift

Uncertain

0.025

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;.;.;.

Vest4

0.38

MutPred

0.82

Gain of glycosylation at T164 (P = 0.0284);.;.;.;

MVP

0.89

MPC

0.28

ClinPred

0.88

GERP RS

4.5

Varity_R

0.24

gMVP

0.46

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