1-158330516-G-C

Position:

• chr1-158330516-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368168.4(CD1B):​c.328+280C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 620,400 control chromosomes in the GnomAD database, including 7,820 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 (1433 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6387 hom.)
• Consequence: CD1B ENST00000368168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD1B	NM_001764.3	c.328+280C>G		intron_variant		ENST00000368168.4	NP_001755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1B	ENST00000368168.4	c.328+280C>G		intron_variant		1	NM_001764.3	ENSP00000357150	P1
CD1B	ENST00000451207.5	c.230+280C>G		intron_variant		3		ENSP00000395161

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18222 AN: 151976 Hom.: 1434 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.120

GnomAD3 exomes AF: 0.167 AC: 17418 AN: 104098 Hom.: 1874 AF XY: 0.172 AC XY: 9525 AN XY: 55490

Gnomad AFR exome AF: 0.0573

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.376

Gnomad SAS exome AF: 0.238

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.148 AC: 69401 AN: 468306 Hom.: 6387 Cov.: 2 AF XY: 0.154 AC XY: 38966 AN XY: 253684

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.120 AC: 18223 AN: 152094 Hom.: 1433 Cov.: 32 AF XY: 0.124 AC XY: 9189 AN XY: 74346

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0796 Hom.: 138

Bravo AF: 0.116

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.60

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: rs962879; hg19: chr1-158300306; COSMIC: COSV63804353;