3-112819829-A-G

Position:

• chr3-112819829-A-G

Variant summary

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

The NM_001199215.3(CD200R1L):​c.683T>C​(p.Phe228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000041 (0 hom.)
• Consequence: CD200R1L NM_001199215.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

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 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=0.10816234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1L	NM_001199215.3	c.683T>C	p.Phe228Ser	missense_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.683T>C	p.Phe228Ser	missense_variant	7/8	5	NM_001199215.3	ENSP00000418413.1
CD200R1L	ENST00000398214.5	c.746T>C	p.Phe249Ser	missense_variant	5/6	1		ENSP00000381272.1
CD200R1L	ENST00000486723.1	n.*745T>C		non_coding_transcript_exon_variant	7/8	2		ENSP00000420461.1
CD200R1L	ENST00000486723.1	n.*745T>C		3_prime_UTR_variant	7/8	2		ENSP00000420461.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459604 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726108

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: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 02, 2021

The c.746T>C (p.F249S) alteration is located in exon 5 (coding exon 5) of the CD200R1L gene. This alteration results from a T to C substitution at nucleotide position 746, causing the phenylalanine (F) at amino acid position 249 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Benign	0.025	T;.;.;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.37	T;T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;D;D;.
REVEL	Benign	0.14
Sift	Benign	0.087	T;T;T;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.16	B;.;.;.
Vest4		0.30
MutPred		0.38		Loss of stability (P = 0.0024);.;.;.;
MVP		0.34
MPC		0.059
ClinPred		0.18	T
GERP RS		3.8
Varity_R		0.13
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

Other links and lift over

dbSNP: rs1260928322; hg19: chr3-112538676;