Variant 1-158255260-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001763.3(CD1A):c.235G>A(p.Glu79Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000884 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

CD1A
NM_001763.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.629

Variant links:

Genes affected

CD1A (HGNC:1634): (CD1a 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 to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

CD1A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18494391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CD1A	NM_001763.3 linkuse as main transcript	c.235G>A	p.Glu79Lys	missense_variant	2/6	ENST00000289429.6
CD1A	NM_001320652.2 linkuse as main transcript	c.202G>A	p.Glu68Lys	missense_variant	2/6
CD1A	XM_024450738.2 linkuse as main transcript	c.-234G>A		5_prime_UTR_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1A	ENST00000289429.6 linkuse as main transcript	c.235G>A	p.Glu79Lys	missense_variant	2/6	1	NM_001763.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000501

AC:

126

AN:

251404

Hom.:

AF XY:

0.000545

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000941

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000918

AC:

1342

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

635

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.000559

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000918

Hom.:

Bravo

AF:

0.000654

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000527

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00124

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.235G>A (p.E79K) alteration is located in exon 2 (coding exon 2) of the CD1A gene. This alteration results from a G to A substitution at nucleotide position 235, causing the glutamic acid (E) at amino acid position 79 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.029

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.056

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0029

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.089

Sift

Benign

0.031

Sift4G

Uncertain

0.0040

Polyphen

0.92

Vest4

0.44

MVP

0.58

MPC

0.28

ClinPred

0.063

GERP RS

4.5

Varity_R

0.68

gMVP

0.39

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