rs366316

Positions:

• chr1-158254492-A-G

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CD1A	NM_001763.3	c.-178A>G		5_prime_UTR_variant	1/6	ENST00000289429.6	NP_001754.2
CD1A	NM_001320652.2	c.26-592A>G		intron_variant			NP_001307581.1
CD1A	XM_024450738.2	c.-410-592A>G		intron_variant			XP_024306506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1A	ENST00000289429	c.-178A>G		5_prime_UTR_variant	1/6	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

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.267

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

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.313

Alfa AF: 0.251 Hom.: 5287

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

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;