1-158354623-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.017 (88 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (82 hom.)
• Consequence: CD1E NM_030893.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100

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 -14 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_single_submitter, 1 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/exons	MANE	UniProt
CD1E	NM_030893.4	c.305A>G	p.His102Arg	missense_variant	2/6	ENST00000368167.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1E	ENST00000368167.8	c.305A>G	p.His102Arg	missense_variant	2/6	1	NM_030893.4	P2

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2638 AN: 152170 Hom.: 88 Cov.: 32

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.: 31 AF XY: 0.00330 AC XY: 446 AN XY: 135232

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.: 82 Cov.: 31 AF XY: 0.00157 AC XY: 1144 AN XY: 727228

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.: 88 Cov.: 32 AF XY: 0.0171 AC XY: 1270 AN XY: 74464

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.: 23

Bravo AF: 0.0200

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0556 AC: 218

ESP6500EA AF: 0.000359 AC: 3

ExAC AF: 0.00509 AC: 616

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.63	T
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	N
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	T
MutationAssessor	Benign	1.6	L;L;L;L;L;L;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.41	T
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	T
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

Other links and lift over

dbSNP: rs2873587; hg19: chr1-158324413; COSMIC: COSV99069280; COSMIC: COSV99069280;