1-158354635-A-T

Variant names:

• chr1-158354635-A-T
• rs1065457
• NM_030893.4:c.317A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030893.4(CD1E):​c.317A>T​(p.Gln106Leu) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD1E NM_030893.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94
• Publications: 42 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07430053).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1E	NM_030893.4	MANE Select	c.317A>T	p.Gln106Leu	missense	Exon 2 of 6	NP_112155.2
	CD1E	NM_001042583.3		c.317A>T	p.Gln106Leu	missense	Exon 2 of 6	NP_001036048.1
	CD1E	NM_001042585.3		c.317A>T	p.Gln106Leu	missense	Exon 2 of 6	NP_001036050.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1E	ENST00000368167.8	TSL:1 MANE Select	c.317A>T	p.Gln106Leu	missense	Exon 2 of 6	ENSP00000357149.3
	CD1E	ENST00000368160.7	TSL:1	c.317A>T	p.Gln106Leu	missense	Exon 2 of 6	ENSP00000357142.3
	CD1E	ENST00000368163.7	TSL:1	c.317A>T	p.Gln106Leu	missense	Exon 2 of 6	ENSP00000357145.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0050
DANN	Benign	0.63
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		-3.9
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.066
Sift	Benign	0.18	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.55		Loss of solvent accessibility (P = 0.0635)
MVP		0.21
MPC		0.056
ClinPred		0.075	T
GERP RS		-5.5
Varity_R		0.073
gMVP		0.31
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1065457; hg19: chr1-158324425;