3-112819893-G-A

Position:

• chr3-112819893-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199215.3(CD200R1L):​c.619C>T​(p.Leu207Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD200R1L NM_001199215.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.45

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-AS1 (HGNC:):

ACMG classification

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=0.05056247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1L	NM_001199215.3	c.619C>T	p.Leu207Phe	missense_variant, splice_region_variant	7/8	ENST00000488794.6	NP_001186144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200R1L	ENST00000488794.6	c.619C>T	p.Leu207Phe	missense_variant, splice_region_variant	7/8	5	NM_001199215.3	ENSP00000418413.1
CD200R1L	ENST00000398214.5	c.682C>T	p.Leu228Phe	missense_variant, splice_region_variant	5/6	1		ENSP00000381272.1
CD200R1L	ENST00000486723.1	n.*681C>T		splice_region_variant, non_coding_transcript_exon_variant	7/8	2		ENSP00000420461.1
CD200R1L	ENST00000486723.1	n.*681C>T		3_prime_UTR_variant	7/8	2		ENSP00000420461.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 03, 2022

The c.682C>T (p.L228F) alteration is located in exon 5 (coding exon 5) of the CD200R1L gene. This alteration results from a C to T substitution at nucleotide position 682, causing the leucine (L) at amino acid position 228 to be replaced by a phenylalanine (F). 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	0.089
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.031
DANN	Benign	0.24
DEOGEN2	Benign	0.0072	T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.39	T;T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.051	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;N;N;.
REVEL	Benign	0.049
Sift	Benign	0.73	T;T;T;.
Sift4G	Benign	0.72	T;T;T;T
Polyphen		0.0040	B;.;.;.
Vest4		0.093
MutPred		0.17		Loss of stability (P = 0.0828);.;.;.;
MVP		0.067
MPC		0.042
ClinPred		0.046	T
GERP RS		-5.3
Varity_R		0.035
gMVP		0.082

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: chr3-112538740;