rs859013

Variant names:

• chr1-158181428-A-G
• rs859013
• NM_001371762.2:c.62-27A>G

Variant summary

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

The NM_001371762.2(CD1D):​c.62-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,607,924 control chromosomes in the GnomAD database, including 19,489 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.12 (1635 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17854 hom.)
• Consequence: CD1D NM_001371762.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 publications found

Genes affected

CD1D (HGNC:1637): (CD1d molecule) This gene encodes a divergent 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1D	NM_001371762.2	c.62-27A>G		intron_variant	Intron 1 of 5	ENST00000674085.2	NP_001358691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1D	ENST00000674085.2	c.62-27A>G		intron_variant	Intron 1 of 5		NM_001371762.2	ENSP00000501100.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18837 AN: 151966 Hom.: 1635 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.167 AC: 41851 AN: 249994 AF XY: 0.174

Gnomad AFR exome AF: 0.0867

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.139 AC: 202789 AN: 1455838 Hom.: 17854 Cov.: 32 AF XY: 0.144 AC XY: 104280 AN XY: 723020

African (AFR) AF: 0.0814 AC: 2718 AN: 33376

American (AMR) AF: 0.129 AC: 5754 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4309 AN: 26102

East Asian (EAS) AF: 0.380 AC: 15009 AN: 39488

South Asian (SAS) AF: 0.330 AC: 28437 AN: 86134

European-Finnish (FIN) AF: 0.122 AC: 6491 AN: 53334

Middle Eastern (MID) AF: 0.136 AC: 714 AN: 5246

European-Non Finnish (NFE) AF: 0.118 AC: 130430 AN: 1107422

Other (OTH) AF: 0.149 AC: 8927 AN: 60090

GnomAD4 genome AF: 0.124 AC: 18844 AN: 152086 Hom.: 1635 Cov.: 32 AF XY: 0.130 AC XY: 9672 AN XY: 74346

African (AFR) AF: 0.0837 AC: 3472 AN: 41504

American (AMR) AF: 0.0975 AC: 1491 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2236 AN: 5142

South Asian (SAS) AF: 0.350 AC: 1683 AN: 4812

European-Finnish (FIN) AF: 0.125 AC: 1319 AN: 10592

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7762 AN: 67966

Other (OTH) AF: 0.103 AC: 217 AN: 2102

Alfa AF: 0.122 Hom.: 821

Bravo AF: 0.117

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.34
PhyloP100		-1.1
La Branchor		0.82
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs859013; hg19: chr1-158151218; COSMIC: COSV63808866; COSMIC: COSV63808866;