Genetic Variant CD38:n.*858C>T (chr4-15849062-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 ENST00000502843.5(CD38):n.*858C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 153,622 control chromosomes in the GnomAD database, including 19,300 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 0.50 ( 19114 hom., cov: 31)

Exomes 𝑓: 0.44 ( 186 hom. )

Consequence

CD38
ENST00000502843.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.683

Publications

12 publications found

Variant links:

Genes affected

CD38 (HGNC:1667): (CD38 molecule) The protein encoded by this gene is a non-lineage-restricted, type II transmembrane glycoprotein that synthesizes and hydrolyzes cyclic adenosine 5'-diphosphate-ribose, an intracellular calcium ion mobilizing messenger. The release of soluble protein and the ability of membrane-bound protein to become internalized indicate both extracellular and intracellular functions for the protein. This protein has an N-terminal cytoplasmic tail, a single membrane-spanning domain, and a C-terminal extracellular region with four N-glycosylation sites. Crystal structure analysis demonstrates that the functional molecule is a dimer, with the central portion containing the catalytic site. It is used as a prognostic marker for patients with chronic lymphocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

CD38 links:

ENSG00000304423 (HGNC:58740):

ENSG00000304423 links:

Genome browser will be placed here

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4 link	c.*460C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000226279.8	NP_001766.2	P28907-1B4E006
CD38	NR_132660.2 link	n.1314C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8 link	c.*460C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001775.4	ENSP00000226279.2		P28907-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75434

AN:

151796

Hom.:

19085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.491

GnomAD4 exome

AF:

0.444

AC:

758

AN:

1708

Hom.:

186

Cov.:

AF XY:

0.446

AC XY:

382

AN XY:

856

show subpopulations

African (AFR)

AF:

0.600

AC:

AN:

American (AMR)

AF:

0.338

AC:

100

AN:

296

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

AN:

East Asian (EAS)

AF:

0.235

AC:

AN:

102

South Asian (SAS)

AF:

0.403

AC:

AN:

134

European-Finnish (FIN)

AF:

0.571

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.486

AC:

503

AN:

1036

Other (OTH)

AF:

0.561

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

111

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:

0.497

AC:

75507

AN:

151914

Hom.:

19114

Cov.:

AF XY:

0.496

AC XY:

36800

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.540

AC:

22374

AN:

41420

American (AMR)

AF:

0.386

AC:

5896

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1511

AN:

3460

East Asian (EAS)

AF:

0.292

AC:

1506

AN:

5152

South Asian (SAS)

AF:

0.469

AC:

2262

AN:

4822

European-Finnish (FIN)

AF:

0.563

AC:

5937

AN:

10552

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34496

AN:

67916

Other (OTH)

AF:

0.487

AC:

1028

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1931

3862

5794

7725

9656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.494

Hom.:

58657

Bravo

AF:

0.485

Asia WGS

AF:

0.410

AC:

1427

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.30

(source)

DANN

Benign

0.34

PhyloP100

-0.68

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over