rs1065457

Positions:

• chr1-158354635-A-G
• chr1-158354635-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368167.8(CD1E):​c.317A>G​(p.Gln106Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,613,352 control chromosomes in the GnomAD database, including 143,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.51 (23277 hom., cov: 32)
  • Exomes 𝑓: 0.39 (120420 hom.)
• Consequence: CD1E ENST00000368167.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0941127E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD1E	NM_030893.4	c.317A>G	p.Gln106Arg	missense_variant	2/6	ENST00000368167.8	NP_112155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1E	ENST00000368167.8	c.317A>G	p.Gln106Arg	missense_variant	2/6	1	NM_030893.4	ENSP00000357149	P2

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78177 AN: 151934 Hom.: 23231 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.445 AC: 110587 AN: 248468 Hom.: 27037 AF XY: 0.442 AC XY: 59622 AN XY: 134854

Gnomad AFR exome AF: 0.829

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.667

Gnomad SAS exome AF: 0.560

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.394 AC: 575075 AN: 1461300 Hom.: 120420 Cov.: 38 AF XY: 0.397 AC XY: 288784 AN XY: 726958

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.432

GnomAD4 genome AF: 0.515 AC: 78286 AN: 152052 Hom.: 23277 Cov.: 32 AF XY: 0.517 AC XY: 38437 AN XY: 74304

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.458

Alfa AF: 0.389 Hom.: 31076

Bravo AF: 0.523

TwinsUK AF: 0.357 AC: 1324

ALSPAC AF: 0.347 AC: 1337

ESP6500AA AF: 0.781 AC: 3006

ESP6500EA AF: 0.344 AC: 2869

ExAC AF: 0.449 AC: 54260

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.91	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0010
DANN	Benign	0.35
DEOGEN2	Benign	0.0056	T;.;.;.;.;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00062	N
LIST_S2	Benign	0.020	T;T;T;T;T;T;T
MetaRNN	Benign	0.0000011	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.37	N;N;N;N;N;N;N
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.97	N;N;N;N;N;N;N
REVEL	Benign	0.063
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B;B
Vest4		0.0050
MPC		0.060
ClinPred		0.0016	T
GERP RS		-5.5
Varity_R		0.025
gMVP		0.12

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: rs1065457; hg19: chr1-158324425; COSMIC: COSV63771281; COSMIC: COSV63771281;