rs859009

Positions:

• chr1-158180338-C-G
• chr1-158180338-C-T

Variant summary

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

The ENST00000368171.5(CD1D):​c.-283-481C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,988 control chromosomes in the GnomAD database, including 1,595 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 (1595 hom., cov: 32)
• Consequence: CD1D ENST00000368171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1D	NM_001371763.1	c.-283-481C>G		intron_variant
CD1D	NM_001766.4	c.-284+176C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1D	ENST00000368171.5	c.-283-481C>G		intron_variant		1		P1
CD1D	ENST00000673723.4	c.-284+176C>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18551 AN: 151870 Hom.: 1596 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18556 AN: 151988 Hom.: 1595 Cov.: 32 AF XY: 0.128 AC XY: 9504 AN XY: 74268

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.102

Alfa AF: 0.107 Hom.: 112

Bravo AF: 0.115

Asia WGS AF: 0.321 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs859009; hg19: chr1-158150128;