rs859013

chr1-158181428-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371762.2(CD1D):c.62-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,607,924 control chromosomes in the GnomAD database, including 19,489 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1635 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17854 hom.)
• Consequence: CD1D NM_001371762.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1D	NM_001371762.2	c.62-27A>G		intron_variant		ENST00000674085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1D	ENST00000674085.2	c.62-27A>G		intron_variant			NM_001371762.2	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18837 AN: 151966 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.167 AC: 41851 AN: 249994 Hom.: 5046 AF XY: 0.174 AC XY: 23525 AN XY: 135334

Gnomad AFR exome AF: 0.0867

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.336

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.139 AC: 202789 AN: 1455838 Hom.: 17854 Cov.: 32 AF XY: 0.144 AC XY: 104280 AN XY: 723020

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.124 AC: 18844 AN: 152086 Hom.: 1635 Cov.: 32 AF XY: 0.130 AC XY: 9672 AN XY: 74346

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.103

Alfa AF: 0.116 Hom.: 309

Bravo AF: 0.117

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.2
Dann	Benign	0.34
La Branchor		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs859013; hg19: chr1-158151218; COSMIC: COSV63808866; COSMIC: COSV63808866;