1-158355993-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_030893.4(CD1E):c.792C>T(p.Asp264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,062 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (4 hom.)
• Consequence: CD1E NM_030893.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.907

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-158355993-C-T is Benign according to our data. Variant chr1-158355993-C-T is described in ClinVar as [Benign]. Clinvar id is 711776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.907 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00506 (770/152176) while in subpopulation AFR AF= 0.0174 (724/41506). AF 95% confidence interval is 0.0164. There are 1 homozygotes in gnomad4. There are 340 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1E	NM_030893.4	c.792C>T	p.Asp264=	synonymous_variant	4/6	ENST00000368167.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1E	ENST00000368167.8	c.792C>T	p.Asp264=	synonymous_variant	4/6	1	NM_030893.4	P2

Frequencies

GnomAD3 genomes AF: 0.00507 AC: 771 AN: 152058 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00149 AC: 374 AN: 251464 Hom.: 2 AF XY: 0.00116 AC XY: 158 AN XY: 135906

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.000867

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000599 AC: 876 AN: 1461886 Hom.: 4 Cov.: 31 AF XY: 0.000536 AC XY: 390 AN XY: 727244

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.000961

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00506 AC: 770 AN: 152176 Hom.: 1 Cov.: 32 AF XY: 0.00457 AC XY: 340 AN XY: 74396

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00295 Hom.: 1

Bravo AF: 0.00601

Asia WGS AF: 0.00144 AC: 6 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.65
Dann	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs73012021; hg19: chr1-158325783; COSMIC: COSV63770529; COSMIC: COSV63770529;