dbSNP rs1800051: CD38:p.Ile168Ile (chr4-15834221-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001775.4(CD38):c.504A>C(p.Ile168Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,596,590 control chromosomes in the GnomAD database, including 2,505 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 0.059 ( 357 hom., cov: 32)

Exomes 𝑓: 0.045 ( 2148 hom. )

Consequence

CD38
NM_001775.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

Publications

14 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP7

Synonymous conserved (PhyloP=0.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4 link	c.504A>C	p.Ile168Ile	synonymous_variant	Exon 4 of 8	ENST00000226279.8	NP_001766.2	P28907-1B4E006
CD38	NR_132660.2 link	n.455A>C		non_coding_transcript_exon_variant	Exon 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8 link	c.504A>C	p.Ile168Ile	synonymous_variant	Exon 4 of 8	1	NM_001775.4	ENSP00000226279.2		P28907-1

Frequencies

GnomAD3 genomes

AF:

0.0585

AC:

8896

AN:

152136

Hom.:

355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0868

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0548

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.0818

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0369

Gnomad OTH

AF:

0.0731

GnomAD2 exomes

AF:

0.0620

AC:

15576

AN:

251324

AF XY:

0.0594

show subpopulations

Gnomad AFR exome

AF:

0.0865

Gnomad AMR exome

AF:

0.0889

Gnomad ASJ exome

AF:

0.0425

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.0304

Gnomad NFE exome

AF:

0.0358

Gnomad OTH exome

AF:

0.0551

GnomAD4 exome

AF:

0.0447

AC:

64492

AN:

1444336

Hom.:

2148

Cov.:

AF XY:

0.0451

AC XY:

32476

AN XY:

719832

show subpopulations

African (AFR)

AF:

0.0892

AC:

2952

AN:

33094

American (AMR)

AF:

0.0843

AC:

3766

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

1072

AN:

26036

East Asian (EAS)

AF:

0.160

AC:

6341

AN:

39572

South Asian (SAS)

AF:

0.0691

AC:

5936

AN:

85848

European-Finnish (FIN)

AF:

0.0304

AC:

1621

AN:

53410

Middle Eastern (MID)

AF:

0.0747

AC:

428

AN:

5732

European-Non Finnish (NFE)

AF:

0.0356

AC:

38972

AN:

1096158

Other (OTH)

AF:

0.0569

AC:

3404

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2882

5764

8647

11529

14411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1624

3248

4872

6496

8120

<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:

0.0585

AC:

8907

AN:

152254

Hom.:

357

Cov.:

AF XY:

0.0583

AC XY:

4341

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0868

AC:

3607

AN:

41538

American (AMR)

AF:

0.0549

AC:

840

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3470

East Asian (EAS)

AF:

0.176

AC:

911

AN:

5168

South Asian (SAS)

AF:

0.0814

AC:

393

AN:

4826

European-Finnish (FIN)

AF:

0.0319

AC:

338

AN:

10612

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0369

AC:

2510

AN:

68016

Other (OTH)

AF:

0.0728

AC:

154

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

413

826

1238

1651

2064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0458

Hom.:

842

Bravo

AF:

0.0629

Asia WGS

AF:

0.141

AC:

490

AN:

3478

EpiCase

AF:

0.0405

EpiControl

AF:

0.0375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.6

(source)

DANN

Benign

0.61

PhyloP100

0.010

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