Variant chr1-158354635-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030893.4(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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.51 ( 23277 hom., cov: 32)

Exomes 𝑓: 0.39 ( 120420 hom. )

Consequence

CD1E
NM_030893.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CD1E	NM_030893.4 link	c.317A>G	p.Gln106Arg	missense_variant	Exon 2 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.317A>G	p.Gln106Arg	missense_variant	Exon 2 of 6	1	NM_030893.4	ENSP00000357149.3		P15812-1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78177

AN:

151934

Hom.:

23231

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.397

AC XY:

288784

AN XY:

726958

show subpopulations

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.:

AF XY:

0.517

AC XY:

38437

AN XY:

74304

show subpopulations

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

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

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

MutationAssessor

Benign

-0.37

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

PrimateAI

Benign

0.25

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over