1-158330050-C-T

Position:

• chr1-158330050-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000368168.4(CD1B):​c.409G>A​(p.Gly137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,940 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (27 hom., cov: 32)
  • Exomes 𝑓: 0.016 (241 hom.)
• Consequence: CD1B ENST00000368168.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 (MetaRNN=0.0115989745).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0124 (1883/152198) while in subpopulation NFE AF= 0.0165 (1119/68000). AF 95% confidence interval is 0.0157. There are 27 homozygotes in gnomad4. There are 958 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD1B	NM_001764.3	c.409G>A	p.Gly137Arg	missense_variant	3/6	ENST00000368168.4	NP_001755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD1B	ENST00000368168.4	c.409G>A	p.Gly137Arg	missense_variant	3/6	1	NM_001764.3	ENSP00000357150	P1
CD1B	ENST00000451207.5	c.313G>A	p.Gly105Arg	missense_variant	2/5	3		ENSP00000395161

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1884 AN: 152080 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0135 AC: 3385 AN: 251296 Hom.: 40 AF XY: 0.0130 AC XY: 1767 AN XY: 135806

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.00867

Gnomad ASJ exome AF: 0.00337

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00346

Gnomad FIN exome AF: 0.0418

Gnomad NFE exome AF: 0.0166

Gnomad OTH exome AF: 0.0184

GnomAD4 exome AF: 0.0163 AC: 23889 AN: 1461742 Hom.: 241 Cov.: 33 AF XY: 0.0158 AC XY: 11491 AN XY: 727176

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.00870

Gnomad4 ASJ exome AF: 0.00375

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00385

Gnomad4 FIN exome AF: 0.0429

Gnomad4 NFE exome AF: 0.0178

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.0124 AC: 1883 AN: 152198 Hom.: 27 Cov.: 32 AF XY: 0.0129 AC XY: 958 AN XY: 74414

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0138 Hom.: 11

Bravo AF: 0.0101

TwinsUK AF: 0.0213 AC: 79

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.0147 AC: 126

ExAC AF: 0.0132 AC: 1598

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0168

EpiControl AF: 0.0147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.4
DANN	Benign	0.78
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.095
Sift	Benign	0.031	D
Sift4G	Uncertain	0.052	T
Polyphen		0.0040	B
Vest4		0.047
MutPred		0.57		Gain of methylation at G137 (P = 0.0275);
MPC		0.015
ClinPred		0.0071	T
GERP RS		-1.4
Varity_R		0.30
gMVP		0.52

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: rs35841099; hg19: chr1-158299840; COSMIC: COSV99069984;