1-158356759-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030893.4(CD1E):c.1030C>T(p.Pro344Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: CD1E NM_030893.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.675

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036773294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1E	NM_030893.4	c.1030C>T	p.Pro344Ser	missense_variant	6/6	ENST00000368167.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1E	ENST00000368167.8	c.1030C>T	p.Pro344Ser	missense_variant	6/6	1	NM_030893.4	P2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 151966 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

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: 0.000353

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000188 AC: 47 AN: 249550 Hom.: 0 AF XY: 0.000162 AC XY: 22 AN XY: 135400

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000388

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000210 AC: 307 AN: 1461786 Hom.: 0 Cov.: 32 AF XY: 0.000204 AC XY: 148 AN XY: 727206

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

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: 0.000267

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome AF: 0.000191 AC: 29 AN: 151966 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74222

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.000506 Hom.: 0

Bravo AF: 0.000193

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000365 AC: 3

ExAC AF: 0.000166 AC: 20

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2023

The c.1030C>T (p.P344S) alteration is located in exon 6 (coding exon 6) of the CD1E gene. This alteration results from a C to T substitution at nucleotide position 1030, causing the proline (P) at amino acid position 344 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.48
Dann	Benign	0.36
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.70	T;T;T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.037	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.68	N;N;N;N;N
REVEL	Benign	0.0060
Sift	Benign	0.52	T;T;T;T;T
Sift4G	Benign	0.74	T;T;T;T;T
Polyphen		0.0040, 0.017, 0.035	.;B;B;B;B
Vest4		0.063
MVP		0.14
MPC		0.066
ClinPred		0.031	T
GERP RS		-3.3
Varity_R		0.021
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs200792123; hg19: chr1-158326549; COSMIC: COSV63770972; COSMIC: COSV63770972;