Genetic Variant ENST00000368171.5:c.-283-553C>T (chr1-158180266-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000368171.5(CD1D):c.-283-553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,226 control chromosomes in the GnomAD database, including 1,605 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.

Frequency

Genomes: 𝑓 0.12 ( 1601 hom., cov: 32)

Exomes 𝑓: 0.27 ( 4 hom. )

Consequence

CD1D
ENST00000368171.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.400

Publications

6 publications found

Variant links:

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]

CD1D links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368171.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	NM_001371763.1		c.-283-553C>T		intron	N/A	NP_001358692.1
	CD1D	NM_001766.4		c.-284+104C>T		intron	N/A	NP_001757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	ENST00000368171.5	TSL:1	c.-283-553C>T		intron	N/A	ENSP00000357153.3
	CD1D	ENST00000673723.4		c.-284+104C>T		intron	N/A	ENSP00000501245.3

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18580

AN:

152038

Hom.:

1602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0786

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0970

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.271

AC:

AN:

Hom.:

AF XY:

0.238

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.269

AC:

AN:

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.122

AC:

18585

AN:

152156

Hom.:

1601

Cov.:

AF XY:

0.128

AC XY:

9517

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0787

AC:

3266

AN:

41504

American (AMR)

AF:

0.0972

AC:

1487

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

615

AN:

3470

East Asian (EAS)

AF:

0.430

AC:

2217

AN:

5154

South Asian (SAS)

AF:

0.349

AC:

1683

AN:

4822

European-Finnish (FIN)

AF:

0.124

AC:

1316

AN:

10572

Middle Eastern (MID)

AF:

0.134

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.114

AC:

7742

AN:

68018

Other (OTH)

AF:

0.101

AC:

214

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

797

1595

2392

3190

3987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.110

Hom.:

1299

Bravo

AF:

0.115

Asia WGS

AF:

0.321

AC:

1115

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.58

PhyloP100

-0.40

PromoterAI

-0.0028

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over