Genetic Variant NM_030893.4:c.650G>A (chr1-158355851-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030893.4(CD1E):c.650G>A(p.Cys217Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C217S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CD1E
NM_030893.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.668

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06556845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1E	NM_030893.4 link	c.650G>A	p.Cys217Tyr	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.650G>A	p.Cys217Tyr	missense_variant	Exon 4 of 6	1	NM_030893.4	ENSP00000357149.3		P15812-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461552

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111822

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.6

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.013

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

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.57

T;T;T;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.066

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;.;.;.;N;.;.;.;.;.;N;N

PhyloP100

-0.67

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.74

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.019

Sift

Benign

0.25

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

Sift4G

Uncertain

0.026

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

Polyphen

0.011, 0.026, 0.0020, 0.28, 0.051, 0.96, 0.0, 0.14, 0.27

.;B;B;B;B;B;B;.;B;D;B;B;B

Vest4

0.10

MutPred

0.38

.;Gain of phosphorylation at C217 (P = 0.0401);.;.;.;Gain of phosphorylation at C217 (P = 0.0401);.;.;.;.;.;Gain of phosphorylation at C217 (P = 0.0401);Gain of phosphorylation at C217 (P = 0.0401);

MVP

0.33

MPC

0.091

ClinPred

0.14

GERP RS

-2.7

PromoterAI

0.0047

Neutral

(source)

Varity_R

0.070

gMVP

0.45

Mutation Taster

=92/8

polymorphism

(source)

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

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NM_030893.4:c.650G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over