rs2269715

Variant names:

• chr1-158255229-C-G
• rs2269715
• NM_001763.3:c.204C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-158255229-C-G
• chr1-158255229-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 25 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1A	NM_001763.3	MANE Select	c.204C>G	p.Cys68Trp	missense	Exon 2 of 6	NP_001754.2	P06126
	CD1A	NM_001320652.2		c.171C>G	p.Cys57Trp	missense	Exon 2 of 6	NP_001307581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1A	ENST00000289429.6	TSL:1 MANE Select	c.204C>G	p.Cys68Trp	missense	Exon 2 of 6	ENSP00000289429.5	P06126
	CD1A	ENST00000894722.1		c.204C>G	p.Cys68Trp	missense	Exon 2 of 6	ENSP00000564781.1
	CD1A	ENST00000894721.1		c.204C>G	p.Cys68Trp	missense	Exon 2 of 6	ENSP00000564780.1

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11592 AN: 152016 Hom.: 810 Cov.: 31

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

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.: 33 AF XY: 0.0843 AC XY: 61287 AN XY: 727230

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

GnomAD4 genome AF: 0.0763 AC: 11602 AN: 152134 Hom.: 808 Cov.: 31 AF XY: 0.0813 AC XY: 6044 AN XY: 74366

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: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0589 AC: 4005 AN: 68004

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.56
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00040	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.00089	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.7	N
PhyloP100		0.014
PrimateAI	Benign	0.28	T
PROVEAN	Benign	4.5	N
REVEL	Benign	0.034
Sift	Benign	0.19	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.053
MPC		0.043
ClinPred		0.0036	T
GERP RS		-1.9
Varity_R		0.083
gMVP		0.46
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2269715; hg19: chr1-158225019; COSMIC: COSV56860848;