Genetic Variant NM_001763.3:c.204C>G (chr1-158255229-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001763.3(CD1A):c.204C>G(p.Cys68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 1,613,996 control chromosomes in the GnomAD database, including 8,420 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.076 ( 808 hom., cov: 31)

Exomes 𝑓: 0.081 ( 7612 hom. )

Consequence

CD1A
NM_001763.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

Publications

25 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.8843703E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1A	NM_001763.3 link	c.204C>G	p.Cys68Trp	missense_variant	Exon 2 of 6	ENST00000289429.6	NP_001754.2	P06126
CD1A	NM_001320652.2 link	c.171C>G	p.Cys57Trp	missense_variant	Exon 2 of 6		NP_001307581.1	P06126
CD1A	XM_024450738.2 link	c.-265C>G		5_prime_UTR_variant	Exon 3 of 7		XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429.6 link	c.204C>G	p.Cys68Trp	missense_variant	Exon 2 of 6	1	NM_001763.3	ENSP00000289429.5		P06126

Frequencies

GnomAD3 genomes

AF:

0.0763

AC:

11592

AN:

152016

Hom.:

810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0717

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.0727

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0589

Gnomad OTH

AF:

0.0569

GnomAD2 exomes

AF:

0.111

AC:

27906

AN:

251456

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.0524

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.0824

Gnomad EAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.0726

Gnomad NFE exome

AF:

0.0569

Gnomad OTH exome

AF:

0.0862

GnomAD4 exome

AF:

0.0806

AC:

117756

AN:

1461862

Hom.:

7612

Cov.:

AF XY:

0.0843

AC XY:

61287

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0542

AC:

1815

AN:

33478

American (AMR)

AF:

0.102

AC:

4576

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

2157

AN:

26136

East Asian (EAS)

AF:

0.336

AC:

13320

AN:

39700

South Asian (SAS)

AF:

0.228

AC:

19662

AN:

86254

European-Finnish (FIN)

AF:

0.0724

AC:

3866

AN:

53420

Middle Eastern (MID)

AF:

0.0990

AC:

571

AN:

5768

European-Non Finnish (NFE)

AF:

0.0598

AC:

66452

AN:

1111986

Other (OTH)

AF:

0.0884

AC:

5337

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

6363

12726

19089

25452

31815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2850

5700

8550

11400

14250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0763

AC:

11602

AN:

152134

Hom.:

808

Cov.:

AF XY:

0.0813

AC XY:

6044

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0517

AC:

2146

AN:

41512

American (AMR)

AF:

0.0720

AC:

1100

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0844

AC:

293

AN:

3470

East Asian (EAS)

AF:

0.378

AC:

1944

AN:

5148

South Asian (SAS)

AF:

0.248

AC:

1192

AN:

4808

European-Finnish (FIN)

AF:

0.0727

AC:

770

AN:

10592

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0589

AC:

4005

AN:

68004

Other (OTH)

AF:

0.0554

AC:

117

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

519

1037

1556

2074

2593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0628

Hom.:

323

Bravo

AF:

0.0727

TwinsUK

AF:

0.0615

AC:

228

ALSPAC

AF:

0.0615

AC:

237

ESP6500AA

AF:

0.0508

AC:

224

ESP6500EA

AF:

0.0577

AC:

496

ExAC

AF:

0.110

AC:

13309

Asia WGS

AF:

0.260

AC:

901

AN:

3478

EpiCase

AF:

0.0573

EpiControl

AF:

0.0572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.3

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.026

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00040

LIST_S2

Benign

0.21

MetaRNN

Benign

0.00089

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.7

PhyloP100

0.014

PrimateAI

Benign

0.28

PROVEAN

Benign

4.5

REVEL

Benign

0.034

Sift

Benign

0.19

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.053

MPC

0.043

ClinPred

0.0036

GERP RS

-1.9

Varity_R

0.083

gMVP

0.46

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over