3-112923721-C-G

Position:

• chr3-112923721-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138806.4(CD200R1):​c.1003G>C​(p.Glu335Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,600,508 control chromosomes in the GnomAD database, including 246,599 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.59 (26610 hom., cov: 31)
  • Exomes 𝑓: 0.55 (219989 hom.)
• Consequence: CD200R1 NM_138806.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0220

Genes affected

CD200R1 (HGNC:24235): (CD200 receptor 1) This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.480122E-5).
• BP6: Variant 3-112923721-C-G is Benign according to our data. Variant chr3-112923721-C-G is described in ClinVar as [Benign]. Clinvar id is 1267119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD200R1	NM_138806.4	c.1003G>C	p.Glu335Gln	missense_variant	8/8	ENST00000308611.8	NP_620161.1
CD200R1	NM_170780.3	c.934G>C	p.Glu312Gln	missense_variant	7/7		NP_740750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD200R1	ENST00000308611.8	c.1003G>C	p.Glu335Gln	missense_variant	8/8	1	NM_138806.4	ENSP00000311035.3
CD200R1	ENST00000471858.5	c.934G>C	p.Glu312Gln	missense_variant	7/7	1		ENSP00000418928.1
CD200R1	ENST00000295863.4	c.*74G>C		3_prime_UTR_variant	4/4	2		ENSP00000295863.4

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89079 AN: 151528 Hom.: 26583 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.563 AC: 138589 AN: 246028 Hom.: 39644 AF XY: 0.563 AC XY: 75059 AN XY: 133316

Gnomad AFR exome AF: 0.696

Gnomad AMR exome AF: 0.551

Gnomad ASJ exome AF: 0.463

Gnomad EAS exome AF: 0.673

Gnomad SAS exome AF: 0.608

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.548 AC: 793624 AN: 1448862 Hom.: 219989 Cov.: 30 AF XY: 0.550 AC XY: 396445 AN XY: 721144

Gnomad4 AFR exome AF: 0.700

Gnomad4 AMR exome AF: 0.559

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.493

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.588 AC: 89146 AN: 151646 Hom.: 26610 Cov.: 31 AF XY: 0.589 AC XY: 43622 AN XY: 74100

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.576

Alfa AF: 0.544 Hom.: 17028

Bravo AF: 0.594

TwinsUK AF: 0.536 AC: 1986

ALSPAC AF: 0.545 AC: 2099

ESP6500AA AF: 0.684 AC: 3013

ESP6500EA AF: 0.533 AC: 4582

ExAC AF: 0.569 AC: 69095

Asia WGS AF: 0.611 AC: 2123 AN: 3476

EpiCase AF: 0.546

EpiControl AF: 0.551

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 23, 2021	This variant is associated with the following publications: (PMID: 31707051) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.046
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00011	N
MetaRNN	Benign	0.000055	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.63	N;N
REVEL	Benign	0.029
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.011
MPC		0.25
ClinPred		0.0038	T
GERP RS		2.5
gMVP		0.14

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: rs9865242; hg19: chr3-112642568; COSMIC: COSV55600751;