rs62642468

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 15/21 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.439

Publications

10 publications found

Variant links:

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]

CD1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD1B	NM_001764.3 link	c.310G>A	p.Gly104Ser	missense_variant	Exon 2 of 6	ENST00000368168.4	NP_001755.1	P29016-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD1B	ENST00000368168.4 link	c.310G>A	p.Gly104Ser	missense_variant	Exon 2 of 6	1	NM_001764.3	ENSP00000357150.3		P29016-1
CD1B	ENST00000451207.5 link	c.211G>A	p.Gly71Ser	missense_variant	Exon 1 of 5	3		ENSP00000395161.1		H7C0I2

Frequencies

GnomAD3 genomes

AF:

0.00989

AC:

1505

AN:

152162

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00931

AC:

2333

AN:

250508

AF XY:

0.00946

show subpopulations

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 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.:

AF XY:

0.0125

AC XY:

9060

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

33474

American (AMR)

AF:

0.0110

AC:

490

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0175

AC:

457

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00292

AC:

252

AN:

86248

European-Finnish (FIN)

AF:

0.00187

AC:

100

AN:

53406

Middle Eastern (MID)

AF:

0.0121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0147

AC:

16383

AN:

1111884

Other (OTH)

AF:

0.0146

AC:

882

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

913

1827

2740

3654

4567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00987

AC:

1503

AN:

152280

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

699

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00289

AC:

120

AN:

41540

American (AMR)

AF:

0.0216

AC:

331

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0138

AC:

936

AN:

68024

Other (OTH)

AF:

0.0128

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0108

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0153

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.00864

AC:

1049

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0175

EpiControl

AF:

0.0172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.98

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.029

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.9

PhyloP100

-0.44

PrimateAI

Benign

0.28

PROVEAN

Benign

3.0

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.13

MVP

0.15

MPC

0.015

ClinPred

0.0043

GERP RS

-2.8

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.097

gMVP

0.34

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over