3-112827537-T-C

Position:

• chr3-112827537-T-C

Variant summary

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

The NM_001199215.3(CD200R1L):​c.197A>G​(p.Glu66Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000027 (0 hom.)
• Consequence: CD200R1L NM_001199215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.326

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]

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=0.13791147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1L	NM_001199215.3	c.197A>G	p.Glu66Gly	missense_variant	5/8	ENST00000488794.6	NP_001186144.1
CD200R1L	NM_001008784.4	c.260A>G	p.Glu87Gly	missense_variant	4/7		NP_001008784.2
CD200R1L	NM_001370552.3	c.197A>G	p.Glu66Gly	missense_variant	6/9		NP_001357481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200R1L	ENST00000488794.6	c.197A>G	p.Glu66Gly	missense_variant	5/8	5	NM_001199215.3	ENSP00000418413.1
CD200R1L	ENST00000398214.5	c.260A>G	p.Glu87Gly	missense_variant	3/6	1		ENSP00000381272.1
CD200R1L	ENST00000486723.1	n.*259A>G		non_coding_transcript_exon_variant	5/8	2		ENSP00000420461.1
CD200R1L	ENST00000486723.1	n.*259A>G		3_prime_UTR_variant	5/8	2		ENSP00000420461.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461882 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727238

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

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

Jun 17, 2024

The c.260A>G (p.E87G) alteration is located in exon 3 (coding exon 3) of the CD200R1L gene. This alteration results from a A to G substitution at nucleotide position 260, causing the glutamic acid (E) at amino acid position 87 to be replaced by a glycine (G). 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	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;.;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.2	D;D;D;.
REVEL	Benign	0.049
Sift	Uncertain	0.0040	D;D;D;.
Sift4G	Benign	0.063	T;T;T;T
Polyphen		0.65	P;.;.;.
Vest4		0.12
MutPred		0.21		Loss of stability (P = 0.0413);.;.;.;
MVP		0.39
MPC		0.14
ClinPred		0.52	D
GERP RS		1.4
Varity_R		0.12
gMVP		0.32

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: chr3-112546384;