chr1-158180329-C-T

Variant names:

• chr1-158180329-C-T
• rs3754471
• ENST00000368171.5:c.-283-490C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368171.5(CD1D):​c.-283-490C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,910 control chromosomes in the GnomAD database, including 10,821 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 0.36 (10821 hom., cov: 31)
• Consequence: CD1D ENST00000368171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	NM_001371763.1		c.-283-490C>T		intron	N/A	NP_001358692.1
	CD1D	NM_001766.4		c.-284+167C>T		intron	N/A	NP_001757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	ENST00000368171.5	TSL:1	c.-283-490C>T		intron	N/A	ENSP00000357153.3
	CD1D	ENST00000673723.4		c.-284+167C>T		intron	N/A	ENSP00000501245.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55122 AN: 151792 Hom.: 10821 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.363 AC: 55132 AN: 151910 Hom.: 10821 Cov.: 31 AF XY: 0.358 AC XY: 26544 AN XY: 74226

African (AFR) AF: 0.225 AC: 9326 AN: 41426

American (AMR) AF: 0.432 AC: 6593 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1676 AN: 5134

South Asian (SAS) AF: 0.232 AC: 1116 AN: 4806

European-Finnish (FIN) AF: 0.386 AC: 4075 AN: 10550

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29887 AN: 67946

Other (OTH) AF: 0.376 AC: 793 AN: 2108

Alfa AF: 0.416 Hom.: 21193

Bravo AF: 0.363

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		-0.0050
PromoterAI		0.0058	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -6

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

Other links and lift over

dbSNP: rs3754471; hg19: chr1-158150119;