rs11574921

Positions:

• chr4-15778735-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.233+88G>A		intron_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.320+88G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.233+88G>A		intron_variant		1	NM_001775.4	ENSP00000226279.2
CD38	ENST00000502843.5	n.233+88G>A		intron_variant		1		ENSP00000427277.1
CD38	ENST00000506191.1	n.350+88G>A		intron_variant		2
CD38	ENST00000511430.1	n.336+88G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9041 AN: 152124 Hom.: 317 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0490

Gnomad4 AMR exome AF: 0.0232

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.0513

Gnomad4 SAS exome AF: 0.0496

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.0628

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0594 AC: 9047 AN: 152242 Hom.: 317 Cov.: 32 AF XY: 0.0620 AC XY: 4614 AN XY: 74444

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0446

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.0541

Alfa AF: 0.0693 Hom.: 54

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
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs11574921; hg19: chr4-15780358;