Genetic Variant NM_001775.4:c.233+88G>A (chr4-15778735-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001775.4(CD38):c.233+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 941,922 control chromosomes in the GnomAD database, including 2,043 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 ( 317 hom., cov: 32)

Exomes 𝑓: 0.062 ( 1726 hom. )

Consequence

CD38
NM_001775.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.372

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4 link	c.233+88G>A		intron_variant	Intron 1 of 7	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2 link	n.320+88G>A		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8 link	c.233+88G>A		intron_variant	Intron 1 of 7	1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9041

AN:

152124

Hom.:

317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0476

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.0447

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0652

Gnomad OTH

AF:

0.0546

GnomAD4 exome

AF:

0.0620

AC:

48940

AN:

789680

Hom.:

1726

AF XY:

0.0612

AC XY:

24797

AN XY:

405446

show subpopulations

African (AFR)

AF:

0.0490

AC:

951

AN:

19424

American (AMR)

AF:

0.0232

AC:

618

AN:

26666

Ashkenazi Jewish (ASJ)

AF:

0.0344

AC:

594

AN:

17248

East Asian (EAS)

AF:

0.0513

AC:

1734

AN:

33784

South Asian (SAS)

AF:

0.0496

AC:

3087

AN:

62248

European-Finnish (FIN)

AF:

0.133

AC:

5147

AN:

38634

Middle Eastern (MID)

AF:

0.0213

AC:

AN:

3472

European-Non Finnish (NFE)

AF:

0.0628

AC:

34607

AN:

551092

Other (OTH)

AF:

0.0573

AC:

2128

AN:

37112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2437

4874

7311

9748

12185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.0594

AC:

9047

AN:

152242

Hom.:

317

Cov.:

AF XY:

0.0620

AC XY:

4614

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0476

AC:

1979

AN:

41568

American (AMR)

AF:

0.0302

AC:

462

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

123

AN:

3470

East Asian (EAS)

AF:

0.0446

AC:

230

AN:

5156

South Asian (SAS)

AF:

0.0473

AC:

228

AN:

4822

European-Finnish (FIN)

AF:

0.135

AC:

1436

AN:

10614

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0652

AC:

4433

AN:

67994

Other (OTH)

AF:

0.0541

AC:

114

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

448

896

1344

1792

2240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0685

Hom.:

Bravo

AF:

0.0492

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.7

(source)

DANN

Benign

0.79

PhyloP100

0.37

PromoterAI

0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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