NM_001763.3:c.-178A>G

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
• Publications: 20 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1A	NM_001763.3	MANE Select	c.-178A>G		5_prime_UTR	Exon 1 of 6	NP_001754.2	P06126
	CD1A	NM_001320652.2		c.26-592A>G		intron	N/A	NP_001307581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1A	ENST00000289429.6	TSL:1 MANE Select	c.-178A>G		5_prime_UTR	Exon 1 of 6	ENSP00000289429.5	P06126
	CD1A	ENST00000894722.1		c.-178A>G		5_prime_UTR	Exon 1 of 6	ENSP00000564781.1
	CD1A	ENST00000894721.1		c.-178A>G		5_prime_UTR	Exon 1 of 6	ENSP00000564780.1

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

African (AFR) AF: 0.527 AC: 14957 AN: 28396

American (AMR) AF: 0.301 AC: 7391 AN: 24544

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 4552 AN: 19112

East Asian (EAS) AF: 0.302 AC: 9920 AN: 32798

South Asian (SAS) AF: 0.310 AC: 20092 AN: 64804

European-Finnish (FIN) AF: 0.253 AC: 7583 AN: 29992

Middle Eastern (MID) AF: 0.242 AC: 1011 AN: 4186

European-Non Finnish (NFE) AF: 0.233 AC: 239356 AN: 1026790

Other (OTH) 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

African (AFR) AF: 0.509 AC: 21058 AN: 41360

American (AMR) AF: 0.286 AC: 4363 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 833 AN: 3460

East Asian (EAS) AF: 0.262 AC: 1342 AN: 5130

South Asian (SAS) AF: 0.313 AC: 1505 AN: 4804

European-Finnish (FIN) AF: 0.257 AC: 2718 AN: 10560

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15878 AN: 67942

Other (OTH) AF: 0.313 AC: 660 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-0.88
PromoterAI		-0.0030	Neutral
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

Other links and lift over

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