rs3796868

Positions:

• chr4-15816768-G-A
• chr4-15816768-G-C

Variant summary

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

The NM_001775.4(CD38):​c.363+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,010,576 control chromosomes in the GnomAD database, including 14,954 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 0.14 (1703 hom., cov: 32)
  • Exomes 𝑓: 0.17 (13251 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.363+128G>A		intron_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.450+128G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.363+128G>A		intron_variant		1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21284 AN: 152050 Hom.: 1705 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.153

GnomAD3 exomes AF: 0.173 AC: 37890 AN: 219068 Hom.: 3373 AF XY: 0.178 AC XY: 21440 AN XY: 120130

Gnomad AFR exome AF: 0.0654

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.137

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.170 AC: 146183 AN: 858408 Hom.: 13251 Cov.: 11 AF XY: 0.175 AC XY: 78612 AN XY: 450428

Gnomad4 AFR exome AF: 0.0681

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.140 AC: 21282 AN: 152168 Hom.: 1703 Cov.: 32 AF XY: 0.142 AC XY: 10557 AN XY: 74394

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.153

Alfa AF: 0.162 Hom.: 3581

Bravo AF: 0.133

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.44

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: rs3796868; hg19: chr4-15818391;