rs6449182

Variant names:

• chr4-15778830-C-G
• rs6449182
• NM_001775.4:c.233+183C>G

Variant summary

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

The NM_001775.4(CD38):​c.233+183C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,182 control chromosomes in the GnomAD database, including 3,713 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 0.21 (3713 hom., cov: 31)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 33 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.233+183C>G		intron_variant	Intron 1 of 7	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.320+183C>G		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.233+183C>G		intron_variant	Intron 1 of 7	1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32374 AN: 151066 Hom.: 3708 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.214 AC: 32400 AN: 151182 Hom.: 3713 Cov.: 31 AF XY: 0.213 AC XY: 15696 AN XY: 73840

African (AFR) AF: 0.251 AC: 10340 AN: 41238

American (AMR) AF: 0.143 AC: 2176 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3464

East Asian (EAS) AF: 0.0164 AC: 83 AN: 5074

South Asian (SAS) AF: 0.167 AC: 798 AN: 4768

European-Finnish (FIN) AF: 0.206 AC: 2133 AN: 10372

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15298 AN: 67716

Other (OTH) AF: 0.199 AC: 419 AN: 2104

Alfa AF: 0.234 Hom.: 553

Bravo AF: 0.211

Asia WGS AF: 0.106 AC: 368 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.61
PhyloP100		-0.82
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: rs6449182; hg19: chr4-15780453;