1-158354623-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030893.4(CD1E):c.305A>G(p.His102Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,614,144 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.017 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 82 hom. )

Consequence

CD1E
NM_030893.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.100

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030742288).

BP6

Variant 1-158354623-A-G is Benign according to our data. Variant chr1-158354623-A-G is described in ClinVar as [Benign]. Clinvar id is 775146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1E	NM_030893.4 link	c.305A>G	p.His102Arg	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.305A>G	p.His102Arg	missense_variant	Exon 2 of 6	1	NM_030893.4	ENSP00000357149.3		P15812-1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2638

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00447

AC:

1115

AN:

249244

Hom.:

AF XY:

0.00330

AC XY:

446

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.0600

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000239

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00184

AC:

2685

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1144

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.00351

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00406

GnomAD4 genome

AF:

0.0173

AC:

2638

AN:

152288

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1270

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0600

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00415

Hom.:

Bravo

AF:

0.0200

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0556

AC:

218

ESP6500EA

AF:

0.000359

AC:

ExAC

AF:

0.00509

AC:

616

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.21

DANN

Benign

0.11

DEOGEN2

Benign

0.017

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.27

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

MetaRNN

Benign

0.0031

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

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;L;L;L;L;L;L

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.2

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

REVEL

Benign

0.037

Sift

Benign

0.36

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

Sift4G

Benign

0.35

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

Polyphen

0.0

B;B;B;B;B;B;B

Vest4

0.20

MVP

0.23

MPC

0.066

ClinPred

0.014

GERP RS

1.2

Varity_R

0.22

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over