rs6449182

chr4-15778830-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CD38	NM_001775.4	c.233+183C>G		intron_variant		ENST00000226279.8
CD38	NR_132660.2	n.320+183C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD38	ENST00000226279.8	c.233+183C>G		intron_variant		1	NM_001775.4	P1
CD38	ENST00000502843.5	c.233+183C>G		intron_variant, NMD_transcript_variant		1
CD38	ENST00000506191.1	n.350+183C>G		intron_variant, non_coding_transcript_variant		2
CD38	ENST00000511430.1	n.336+183C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.199

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

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: rs6449182; hg19: chr4-15780453;