rs11574930

Positions:

• chr4-15840268-C-A

Variant summary

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

The NM_001775.4(CD38):​c.752+150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 729,280 control chromosomes in the GnomAD database, including 678 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 0.045 (487 hom., cov: 31)
  • Exomes 𝑓: 0.0069 (191 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577

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 (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.752+150C>A		intron_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.703+150C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.752+150C>A		intron_variant		1	NM_001775.4	ENSP00000226279.2
CD38	ENST00000502843.5	n.*247+150C>A		intron_variant		1		ENSP00000427277.1
CD38	ENST00000510674.1	c.416+150C>A		intron_variant		5		ENSP00000423047.1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6819 AN: 152098 Hom.: 486 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.0307

GnomAD4 exome AF: 0.00692 AC: 3996 AN: 577064 Hom.: 191 AF XY: 0.00629 AC XY: 1933 AN XY: 307378

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.00355

Gnomad4 EAS exome AF: 0.0000292

Gnomad4 SAS exome AF: 0.00468

Gnomad4 FIN exome AF: 0.0000837

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.0449 AC: 6842 AN: 152216 Hom.: 487 Cov.: 31 AF XY: 0.0437 AC XY: 3249 AN XY: 74428

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0285 Hom.: 45

Bravo AF: 0.0508

Asia WGS AF: 0.00982 AC: 34 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	3.3
DANN	Benign	0.28

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

LitVar

Other links and lift over

dbSNP: rs11574930; hg19: chr4-15841891;