chr1-158355534-T-C

Variant names:

• chr1-158355534-T-C
• rs192732251
• NM_030893.4:c.590T>C

Variant summary

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

The NM_030893.4(CD1E):​c.590T>C​(p.Leu197Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CD1E NM_030893.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 0 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.590T>C	p.Leu197Pro	missense	Exon 3 of 6	NP_112155.2	P15812-1
	CD1E	NM_001042583.3		c.590T>C	p.Leu197Pro	missense	Exon 3 of 6	NP_001036048.1	P15812-2
	CD1E	NM_001042585.3		c.590T>C	p.Leu197Pro	missense	Exon 3 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.590T>C	p.Leu197Pro	missense	Exon 3 of 6	ENSP00000357149.3	P15812-1
	CD1E	ENST00000368160.7	TSL:1	c.590T>C	p.Leu197Pro	missense	Exon 3 of 6	ENSP00000357142.3	P15812-2
	CD1E	ENST00000368163.7	TSL:1	c.590T>C	p.Leu197Pro	missense	Exon 3 of 6	ENSP00000357145.3	P15812-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249380 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000752 AC: 11 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111994

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41540

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	0.027
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		2.1
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.96	P
Vest4		0.74
MVP		0.58
MPC		0.45
ClinPred		0.55	D
GERP RS		3.4
PromoterAI		-0.013	Neutral
Varity_R		0.96
gMVP		0.81
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs192732251; hg19: chr1-158325324;