rs2286553

Variant names:

• chr4-15834360-C-T
• rs2286553
• NM_001775.4:c.585+58C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001775.4(CD38):​c.585+58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 998,972 control chromosomes in the GnomAD database, including 1,914 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 (363 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1551 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 6 publications found

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]

ENSG00000304423 (HGNC:58740):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.585+58C>T		intron_variant	Intron 4 of 7	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.536+58C>T		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.585+58C>T		intron_variant	Intron 4 of 7	1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8945 AN: 152128 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0727

GnomAD4 exome AF: 0.0492 AC: 41641 AN: 846726 Hom.: 1551 AF XY: 0.0494 AC XY: 21999 AN XY: 445692

African (AFR) AF: 0.0891 AC: 1909 AN: 21416

American (AMR) AF: 0.0851 AC: 3671 AN: 43152

Ashkenazi Jewish (ASJ) AF: 0.0416 AC: 920 AN: 22128

East Asian (EAS) AF: 0.160 AC: 5891 AN: 36910

South Asian (SAS) AF: 0.0693 AC: 5070 AN: 73138

European-Finnish (FIN) AF: 0.0303 AC: 1605 AN: 52936

Middle Eastern (MID) AF: 0.0778 AC: 356 AN: 4574

European-Non Finnish (NFE) AF: 0.0361 AC: 19927 AN: 552346

Other (OTH) AF: 0.0571 AC: 2292 AN: 40126

GnomAD4 genome AF: 0.0588 AC: 8956 AN: 152246 Hom.: 363 Cov.: 32 AF XY: 0.0586 AC XY: 4362 AN XY: 74438

African (AFR) AF: 0.0876 AC: 3638 AN: 41532

American (AMR) AF: 0.0552 AC: 845 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.178 AC: 923 AN: 5180

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4822

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0369 AC: 2512 AN: 68032

Other (OTH) AF: 0.0724 AC: 153 AN: 2112

Alfa AF: 0.0484 Hom.: 40

Bravo AF: 0.0631

Asia WGS AF: 0.142 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		0.090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2286553; hg19: chr4-15835983; COSMIC: COSV56890493;