rs200189250

Variant names:

• chr1-158354541-C-G
• rs200189250
• NM_030893.4:c.223C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-158354541-C-G
• chr1-158354541-C-T

Variant summary

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

The NM_030893.4(CD1E):​c.223C>G​(p.Arg75Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CD1E NM_030893.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854

Genes affected

CD1E (HGNC:1638): (CD1e molecule) This gene encodes a member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes within Golgi compartments, endosomes, and lysosomes, and is cleaved into a stable soluble form. The soluble form is required for the intracellular processing of some glycolipids into a form that can be presented by other CD1 family members. Many alternatively spliced transcript variants encoding different isoforms have been described. Additional transcript variants have been found; however, their biological validity has not been determined. [provided by RefSeq, Jun 2010]

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=0.0965938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1E	NM_030893.4	c.223C>G	p.Arg75Gly	missense_variant	Exon 2 of 6	ENST00000368167.8	NP_112155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1E	ENST00000368167.8	c.223C>G	p.Arg75Gly	missense_variant	Exon 2 of 6	1	NM_030893.4	ENSP00000357149.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74306

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.0
DANN	Benign	0.91
DEOGEN2	Benign	0.027	T;.;.;.;.;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.39	T;T;T;T;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.097	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M;M;M
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D;D
REVEL	Benign	0.050
Sift	Benign	0.28	T;D;T;D;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T;T;T
Polyphen		0.015	B;B;B;D;B;P;B
Vest4		0.38
MutPred		0.52		Loss of MoRF binding (P = 0.0591);Loss of MoRF binding (P = 0.0591);Loss of MoRF binding (P = 0.0591);Loss of MoRF binding (P = 0.0591);Loss of MoRF binding (P = 0.0591);Loss of MoRF binding (P = 0.0591);Loss of MoRF binding (P = 0.0591);
MVP		0.30
MPC		0.17
ClinPred		0.11	T
GERP RS		-3.4
Varity_R		0.29
gMVP		0.44

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: rs200189250; hg19: chr1-158324331;