dbSNP rs73012021: CD1E:p.Asp264Glu (chr1-158355993-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_030893.4(CD1E):c.792C>A(p.Asp264Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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. Synonymous variant affecting the same amino acid position (i.e. D264D) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD1E
NM_030893.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.907

Variant links:

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]

CD1E links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1E	NM_030893.4 link	c.792C>A	p.Asp264Glu	missense_variant	Exon 4 of 6	ENST00000368167.8	NP_112155.2	P15812-1A2RRL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1E	ENST00000368167.8 link	c.792C>A	p.Asp264Glu	missense_variant	Exon 4 of 6	1	NM_030893.4	ENSP00000357149.3		P15812-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

1.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

.;T;.;.;.;.;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.022

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D;D;T

M_CAP

Benign

0.0053

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

4.1

.;H;.;.;.;.;.;H;H

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

D;D;D;D;D;D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D;D;D

Polyphen

1.0, 0.97, 1.0

.;D;D;D;D;D;D;D;D

Vest4

0.83

MutPred

0.80

.;Gain of sheet (P = 0.0827);.;.;.;.;.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.38

MPC

0.32

ClinPred

1.0

GERP RS

-2.1

Varity_R

0.70

gMVP

0.79

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over