rs366316

Variant names:

• chr1-158254492-A-G
• rs366316
• NM_001763.3:c.-178A>G

Variant summary

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

The NM_001763.3(CD1A):​c.-178A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,435,194 control chromosomes in the GnomAD database, including 50,517 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 0.32 (8959 hom., cov: 29)
  • Exomes 𝑓: 0.25 (41558 hom.)
• Consequence: CD1A NM_001763.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

Genes affected

CD1A (HGNC:1634): (CD1a molecule) This gene encodes a 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 the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1A	NM_001763.3	c.-178A>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000289429.6	NP_001754.2
CD1A	NM_001320652.2	c.26-592A>G		intron_variant	Intron 1 of 5		NP_001307581.1
CD1A	XM_024450738.2	c.-410-592A>G		intron_variant	Intron 2 of 6		XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429	c.-178A>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_001763.3	ENSP00000289429.5

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48654 AN: 151694 Hom.: 8944 Cov.: 29

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.249 AC: 318941 AN: 1283382 Hom.: 41558 Cov.: 32 AF XY: 0.250 AC XY: 156078 AN XY: 624964

Gnomad4 AFR exome AF: 0.527 AC: 14957 AN: 28396

Gnomad4 AMR exome AF: 0.301 AC: 7391 AN: 24544

Gnomad4 ASJ exome AF: 0.238 AC: 4552 AN: 19112

Gnomad4 EAS exome AF: 0.302 AC: 9920 AN: 32798

Gnomad4 SAS exome AF: 0.310 AC: 20092 AN: 64804

Gnomad4 FIN exome AF: 0.253 AC: 7583 AN: 29992

Gnomad4 NFE exome AF: 0.233 AC: 239356 AN: 1026790

Gnomad4 Remaining exome AF: 0.267 AC: 14079 AN: 52760

GnomAD4 genome AF: 0.321 AC: 48711 AN: 151812 Hom.: 8959 Cov.: 29 AF XY: 0.320 AC XY: 23727 AN XY: 74190

Gnomad4 AFR AF: 0.509 AC: 0.509139 AN: 0.509139

Gnomad4 AMR AF: 0.286 AC: 0.286249 AN: 0.286249

Gnomad4 ASJ AF: 0.241 AC: 0.240751 AN: 0.240751

Gnomad4 EAS AF: 0.262 AC: 0.261598 AN: 0.261598

Gnomad4 SAS AF: 0.313 AC: 0.313281 AN: 0.313281

Gnomad4 FIN AF: 0.257 AC: 0.257386 AN: 0.257386

Gnomad4 NFE AF: 0.234 AC: 0.233699 AN: 0.233699

Gnomad4 OTH AF: 0.313 AC: 0.312796 AN: 0.312796

Alfa AF: 0.263 Hom.: 8570

Bravo AF: 0.329

Asia WGS AF: 0.345 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.51
Mutation Taster		=300/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs366316; hg19: chr1-158224282; COSMIC: COSV56861201;