rs859008

Positions:

• chr1-158180266-C-T

Variant summary

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

The ENST00000368171.5(CD1D):​c.-283-553C>T 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 152,226 control chromosomes in the GnomAD database, including 1,605 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 (1601 hom., cov: 32)
  • Exomes 𝑓: 0.27 (4 hom.)
• Consequence: CD1D ENST00000368171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD1D	NM_001371763.1	c.-283-553C>T		intron_variant
CD1D	NM_001766.4	c.-284+104C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD1D	ENST00000368171.5	c.-283-553C>T		intron_variant		1		P1
CD1D	ENST00000673723.4	c.-284+104C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18580 AN: 152038 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.271 AC: 19 AN: 70 Hom.: 4 AF XY: 0.238 AC XY: 10 AN XY: 42

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.122 AC: 18585 AN: 152156 Hom.: 1601 Cov.: 32 AF XY: 0.128 AC XY: 9517 AN XY: 74362

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.0972

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.101

Alfa AF: 0.111 Hom.: 1022

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	-0.91
CADD	Benign	1.1
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs859008; hg19: chr1-158150056;