rs12033535

Variant names:

• chr1-158286506-T-C
• rs12033535
• XM_017002785.3:c.*1421A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The XM_017002785.3(CD1B):​c.*1421A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 152,306 control chromosomes in the GnomAD database, including 123 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 0.035 (123 hom., cov: 32)
• Consequence: CD1B XM_017002785.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557
• Publications: 6 publications found

Genes affected

CD1B (HGNC:1635): (CD1b 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 late endosomes and lysosomes via a tyrosine-based motif in the cytoplasmic tail, and requires vesicular acidification to bind lipid antigens. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0347 (5279/152306) while in subpopulation EAS AF = 0.0524 (271/5170). AF 95% confidence interval is 0.0473. There are 123 homozygotes in GnomAd4. There are 2645 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1B	XM_017002785.3	c.*1421A>G		3_prime_UTR_variant	Exon 4 of 4		XP_016858274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5278 AN: 152188 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.00900

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0347 AC: 5279 AN: 152306 Hom.: 123 Cov.: 32 AF XY: 0.0355 AC XY: 2645 AN XY: 74480

African (AFR) AF: 0.00907 AC: 377 AN: 41580

American (AMR) AF: 0.0271 AC: 414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.0524 AC: 271 AN: 5170

South Asian (SAS) AF: 0.0375 AC: 181 AN: 4830

European-Finnish (FIN) AF: 0.0762 AC: 809 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 2999 AN: 68026

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0368 Hom.: 292

Bravo AF: 0.0305

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.43
PhyloP100		0.56

Splicing

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

Other links and lift over

dbSNP: rs12033535; hg19: chr1-158256296;