1-158182073-C-G

Variant names:

• chr1-158182073-C-G
• rs1648457513
• NM_001371762.2:c.370C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371762.2(CD1D):​c.370C>G​(p.Pro124Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P124S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD1D NM_001371762.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 0 publications found

Genes affected

CD1D (HGNC:1637): (CD1d molecule) This gene encodes a divergent 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 late endosomes and lysosomes via a tyrosine-based motif in the cytoplasmic tail. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075786084).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371762.2. 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
	CD1D	NM_001371762.2	MANE Select	c.370C>G	p.Pro124Ala	missense	Exon 3 of 6	NP_001358691.1	P15813
	CD1D	NM_001371763.1		c.370C>G	p.Pro124Ala	missense	Exon 4 of 7	NP_001358692.1	P15813
	CD1D	NM_001766.4		c.370C>G	p.Pro124Ala	missense	Exon 4 of 7	NP_001757.1	P15813

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	ENST00000674085.2	MANE Select	c.370C>G	p.Pro124Ala	missense	Exon 3 of 6	ENSP00000501100.1	P15813
	CD1D	ENST00000368171.5	TSL:1	c.370C>G	p.Pro124Ala	missense	Exon 4 of 7	ENSP00000357153.3	P15813
	CD1D	ENST00000866546.1		c.370C>G	p.Pro124Ala	missense	Exon 4 of 7	ENSP00000536605.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461328 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726954

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111642

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.047
DANN	Benign	0.52
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.0090
Sift	Benign	0.32	T
Sift4G	Benign	0.74	T
Polyphen		0.078	B
Vest4		0.17
MutPred		0.46		Gain of catalytic residue at P124 (P = 0.0098)
MVP		0.29
MPC		0.15
ClinPred		0.16	T
GERP RS		1.8
Varity_R		0.13
gMVP		0.22
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1648457513; hg19: chr1-158151863;