NM_030893.4:c.698C>G

Variant names:

• chr1-158355899-C-G
• rs201152862
• NM_030893.4:c.698C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030893.4(CD1E):​c.698C>G​(p.Ser233*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD1E NM_030893.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030893.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1E	NM_030893.4	MANE Select	c.698C>G	p.Ser233*	stop_gained	Exon 4 of 6	NP_112155.2	P15812-1
	CD1E	NM_001042583.3		c.698C>G	p.Ser233*	stop_gained	Exon 4 of 6	NP_001036048.1	P15812-2
	CD1E	NM_001042585.3		c.698C>G	p.Ser233*	stop_gained	Exon 4 of 6	NP_001036050.1	P15812-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1E	ENST00000368167.8	TSL:1 MANE Select	c.698C>G	p.Ser233*	stop_gained	Exon 4 of 6	ENSP00000357149.3	P15812-1
	CD1E	ENST00000368160.7	TSL:1	c.698C>G	p.Ser233*	stop_gained	Exon 4 of 6	ENSP00000357142.3	P15812-2
	CD1E	ENST00000368163.7	TSL:1	c.698C>G	p.Ser233*	stop_gained	Exon 4 of 6	ENSP00000357145.3	P15812-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.83
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Benign	0.43	N
PhyloP100		4.3
Vest4		0.78
GERP RS		4.8
PromoterAI		-0.0015	Neutral
Mutation Taster		=38/162	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201152862; hg19: chr1-158325689;