1-158180389-A-T

Variant names:

• chr1-158180389-A-T
• rs859010
• ENST00000368171.5:c.-283-430A>T

Variant summary

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

The ENST00000368171.5(CD1D):​c.-283-430A>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 151,938 control chromosomes in the GnomAD database, including 1,581 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 (1581 hom., cov: 32)
• Consequence: CD1D ENST00000368171.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 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.-283-430A>T		intron	N/A	NP_001358692.1
	CD1D	NM_001766.4		c.-284+227A>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.-283-430A>T		intron	N/A	ENSP00000357153.3
	CD1D	ENST00000673723.4		c.-284+227A>T		intron	N/A	ENSP00000501245.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18496 AN: 151818 Hom.: 1581 Cov.: 32

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.122 AC: 18503 AN: 151938 Hom.: 1581 Cov.: 32 AF XY: 0.127 AC XY: 9465 AN XY: 74248

African (AFR) AF: 0.0785 AC: 3255 AN: 41466

American (AMR) AF: 0.0969 AC: 1480 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 615 AN: 3460

East Asian (EAS) AF: 0.428 AC: 2188 AN: 5112

South Asian (SAS) AF: 0.347 AC: 1662 AN: 4786

European-Finnish (FIN) AF: 0.124 AC: 1309 AN: 10564

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7733 AN: 67958

Other (OTH) AF: 0.101 AC: 214 AN: 2110

Alfa AF: 0.102 Hom.: 108

Bravo AF: 0.115

Asia WGS AF: 0.321 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.65
PhyloP100		-3.8
PromoterAI		-0.0094	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs859010; hg19: chr1-158150179;