1-158181715-T-G

Position:

• chr1-158181715-T-G

Variant summary

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

The NM_001371762.2(CD1D):​c.322T>G​(p.Leu108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,608,584 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: CD1D NM_001371762.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.60

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]

CD1D (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD1D	NM_001371762.2	c.322T>G	p.Leu108Val	missense_variant	2/6	ENST00000674085.2	NP_001358691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1D	ENST00000674085.2	c.322T>G	p.Leu108Val	missense_variant	2/6		NM_001371762.2	ENSP00000501100.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152154 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000249 AC: 61 AN: 244602 Hom.: 1 AF XY: 0.000263 AC XY: 35 AN XY: 133088

Gnomad AFR exome AF: 0.000128

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0000582

Gnomad NFE exome AF: 0.000365

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000242 AC: 353 AN: 1456312 Hom.: 1 Cov.: 32 AF XY: 0.000239 AC XY: 173 AN XY: 724732

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.000355

Gnomad4 NFE exome AF: 0.000257

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152272 Hom.: 1 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74464

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.000170

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000206 AC: 25

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.322T>G (p.L108V) alteration is located in exon 3 (coding exon 2) of the CD1D gene. This alteration results from a T to G substitution at nucleotide position 322, causing the leucine (L) at amino acid position 108 to be replaced by a valine (V). 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	0.087
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.014
DANN	Benign	0.64
DEOGEN2	Benign	0.088	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.012
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.0070	B
Vest4		0.090
MVP		0.12
MPC		0.16
ClinPred		0.023	T
GERP RS		-8.7
Varity_R		0.16
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145209409; hg19: chr1-158151505;