1-158330050-C-T

Variant names:

• chr1-158330050-C-T
• rs35841099
• NM_001764.3:c.409G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001764.3(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. 14/21 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 NM_001764.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 9 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 (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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1B	NM_001764.3	MANE Select	c.409G>A	p.Gly137Arg	missense	Exon 3 of 6	NP_001755.1	P29016-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1B	ENST00000368168.4	TSL:1 MANE Select	c.409G>A	p.Gly137Arg	missense	Exon 3 of 6	ENSP00000357150.3	P29016-1
	CD1B	ENST00000451207.5	TSL:3	c.310G>A	p.Gly104Arg	missense	Exon 2 of 5	ENSP00000395161.1	H7C0I2
	CD1B	ENST00000902884.1		c.409G>A	p.Gly137Arg	missense	Exon 3 of 5	ENSP00000572943.1

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

GnomAD2 exomes AF: 0.0135 AC: 3385 AN: 251296 AF XY: 0.0130

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 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

African (AFR) AF: 0.00191 AC: 64 AN: 33472

American (AMR) AF: 0.00870 AC: 389 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 98 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00385 AC: 332 AN: 86254

European-Finnish (FIN) AF: 0.0429 AC: 2292 AN: 53414

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.0178 AC: 19738 AN: 1111904

Other (OTH) AF: 0.0159 AC: 959 AN: 60384

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

African (AFR) AF: 0.00262 AC: 109 AN: 41532

American (AMR) AF: 0.0108 AC: 165 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4810

European-Finnish (FIN) AF: 0.0377 AC: 400 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0165 AC: 1119 AN: 68000

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.0135 Hom.: 33

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 v4.9

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
PhyloP100		-1.2
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
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: rs35841099; hg19: chr1-158299840; COSMIC: COSV99069984;