chr1-158182293-C-T

Variant names:

• chr1-158182293-C-T
• rs149463702
• NM_001371762.2:c.590C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371762.2(CD1D):​c.590C>T​(p.Ser197Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: CD1D NM_001371762.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0390
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03945732).

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.590C>T	p.Ser197Leu	missense	Exon 3 of 6	NP_001358691.1	P15813
	CD1D	NM_001371763.1		c.590C>T	p.Ser197Leu	missense	Exon 4 of 7	NP_001358692.1	P15813
	CD1D	NM_001766.4		c.590C>T	p.Ser197Leu	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.590C>T	p.Ser197Leu	missense	Exon 3 of 6	ENSP00000501100.1	P15813
	CD1D	ENST00000368171.5	TSL:1	c.590C>T	p.Ser197Leu	missense	Exon 4 of 7	ENSP00000357153.3	P15813
	CD1D	ENST00000866546.1		c.590C>T	p.Ser197Leu	missense	Exon 4 of 7	ENSP00000536605.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000760 AC: 19 AN: 250080 AF XY: 0.0000739

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14 AN XY: 727222

African (AFR) AF: 0.000777 AC: 26 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74444

African (AFR) AF: 0.000794 AC: 33 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-0.039
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.038
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.010	D
Polyphen		0.77	P
Vest4		0.12
MVP		0.33
MPC		0.17
ClinPred		0.15	T
GERP RS		0.14
Varity_R		0.25
gMVP		0.30
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149463702; hg19: chr1-158152083; COSMIC: COSV63809178; COSMIC: COSV63809178;