rs12644506

Variant names:

• chr4-15798255-C-T
• rs12644506
• NM_001775.4:c.234-18256C>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.234-18256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,184 control chromosomes in the GnomAD database, including 277 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 0.053 (277 hom., cov: 32)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.234-18256C>T		intron_variant	Intron 1 of 7	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.321-18256C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.234-18256C>T		intron_variant	Intron 1 of 7	1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8011 AN: 152066 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0516

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0527 AC: 8014 AN: 152184 Hom.: 277 Cov.: 32 AF XY: 0.0553 AC XY: 4114 AN XY: 74400

African (AFR) AF: 0.0232 AC: 963 AN: 41542

American (AMR) AF: 0.0277 AC: 423 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 123 AN: 3464

East Asian (EAS) AF: 0.0457 AC: 236 AN: 5168

South Asian (SAS) AF: 0.0487 AC: 234 AN: 4808

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10586

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0654 AC: 4444 AN: 68002

Other (OTH) AF: 0.0511 AC: 108 AN: 2114

Alfa AF: 0.0604 Hom.: 466

Bravo AF: 0.0413

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.67
DANN	Benign	0.62
PhyloP100		-0.77
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: rs12644506; hg19: chr4-15799878;