1-158330516-G-C

Variant names:

• chr1-158330516-G-C
• rs962879
• NM_001764.3:c.328+280C>G

Variant summary

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

The NM_001764.3(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 NM_001764.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001764.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1B	NM_001764.3	MANE Select	c.328+280C>G		intron	N/A	NP_001755.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1B	ENST00000368168.4	TSL:1 MANE Select	c.328+280C>G		intron	N/A	ENSP00000357150.3
	CD1B	ENST00000451207.5	TSL:3	c.229+280C>G		intron	N/A	ENSP00000395161.1

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

GnomAD2 exomes AF: 0.167 AC: 17418 AN: 104098 AF XY: 0.172

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 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

African (AFR) AF: 0.0550 AC: 759 AN: 13808

American (AMR) AF: 0.139 AC: 4027 AN: 28960

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 2250 AN: 16074

East Asian (EAS) AF: 0.341 AC: 9175 AN: 26900

South Asian (SAS) AF: 0.236 AC: 12931 AN: 54708

European-Finnish (FIN) AF: 0.108 AC: 2840 AN: 26240

Middle Eastern (MID) AF: 0.171 AC: 621 AN: 3628

European-Non Finnish (NFE) AF: 0.122 AC: 33078 AN: 271776

Other (OTH) AF: 0.142 AC: 3720 AN: 26212

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

African (AFR) AF: 0.0539 AC: 2236 AN: 41510

American (AMR) AF: 0.140 AC: 2134 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1935 AN: 5126

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4814

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10564

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8586 AN: 68002

Other (OTH) AF: 0.119 AC: 251 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.60
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs962879; hg19: chr1-158300306; COSMIC: COSV63804353;