NM_030893.4:c.584C>G

Variant names:

• chr1-158355528-C-G
• rs199846351
• NM_030893.4:c.584C>G

Variant summary

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

The NM_030893.4(CD1E):​c.584C>G​(p.Ala195Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,852 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. 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. A195V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CD1E NM_030893.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=0.13434342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1E	NM_030893.4	c.584C>G	p.Ala195Gly	missense_variant	Exon 3 of 6	ENST00000368167.8	NP_112155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1E	ENST00000368167.8	c.584C>G	p.Ala195Gly	missense_variant	Exon 3 of 6	1	NM_030893.4	ENSP00000357149.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249388 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135330

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.026	.;T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.24	T;T;T;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.85	.;L;L;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.0060
Sift	Benign	0.088	T;T;T;T;T
Sift4G	Benign	0.33	T;T;T;T;T
Polyphen		0.0030, 0.0010, 0.21, 0.19	.;B;B;B;B
Vest4		0.26
MutPred		0.44		.;Loss of stability (P = 0.1061);Loss of stability (P = 0.1061);Loss of stability (P = 0.1061);Loss of stability (P = 0.1061);
MVP		0.36
MPC		0.057
ClinPred		0.056	T
GERP RS		-0.049
Varity_R		0.21
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs199846351; hg19: chr1-158325318;