rs62642468

Positions:

• chr1-158330814-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001764.3(CD1B):​c.310G>A​(p.Gly104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,614,004 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (15 hom., cov: 32)
  • Exomes 𝑓: 0.013 (145 hom.)
• Consequence: CD1B NM_001764.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.439

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028293729).
• BP6: Variant 1-158330814-C-T is Benign according to our data. Variant chr1-158330814-C-T is described in ClinVar as [Benign]. Clinvar id is 770494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00987 (1503/152280) while in subpopulation AMR AF= 0.0216 (331/15306). AF 95% confidence interval is 0.0197. There are 15 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD1B	NM_001764.3	c.310G>A	p.Gly104Ser	missense_variant	2/6	ENST00000368168.4	NP_001755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1B	ENST00000368168.4	c.310G>A	p.Gly104Ser	missense_variant	2/6	1	NM_001764.3	ENSP00000357150	P1
CD1B	ENST00000451207.5	c.214G>A	p.Gly72Ser	missense_variant	1/5	3		ENSP00000395161

Frequencies

GnomAD3 genomes AF: 0.00989 AC: 1505 AN: 152162 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00931 AC: 2333 AN: 250508 Hom.: 25 AF XY: 0.00946 AC XY: 1282 AN XY: 135488

Gnomad AFR exome AF: 0.00272

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.0168

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.0128 AC: 18707 AN: 1461724 Hom.: 145 Cov.: 32 AF XY: 0.0125 AC XY: 9060 AN XY: 727168

Gnomad4 AFR exome AF: 0.00215

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0175

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00292

Gnomad4 FIN exome AF: 0.00187

Gnomad4 NFE exome AF: 0.0147

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.00987 AC: 1503 AN: 152280 Hom.: 15 Cov.: 32 AF XY: 0.00939 AC XY: 699 AN XY: 74480

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0128 Hom.: 28

Bravo AF: 0.0108

TwinsUK AF: 0.0156 AC: 58

ALSPAC AF: 0.0153 AC: 59

ESP6500AA AF: 0.00363 AC: 16

ESP6500EA AF: 0.0155 AC: 133

ExAC AF: 0.00864 AC: 1049

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0175

EpiControl AF: 0.0172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.98
DANN	Benign	0.41
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.9	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	3.0	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.15
MPC		0.015
ClinPred		0.0043	T
GERP RS		-2.8
Varity_R		0.097
gMVP		0.34

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: rs62642468; hg19: chr1-158300604;