4-15839216-A-G

Variant names:

• chr4-15839216-A-G
• rs10805347
• NM_001775.4:c.660-810A>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.660-810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 151,912 control chromosomes in the GnomAD database, including 41,622 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 0.73 (41622 hom., cov: 29)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• Publications: 10 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	NM_001775.4	MANE Select	c.660-810A>G		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.611-810A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.660-810A>G		intron	N/A	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.*155-810A>G		intron	N/A	ENSP00000427277.1
	CD38	ENST00000510674.1	TSL:5	c.324-810A>G		intron	N/A	ENSP00000423047.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110371 AN: 151794 Hom.: 41577 Cov.: 29

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.727 AC: 110468 AN: 151912 Hom.: 41622 Cov.: 29 AF XY: 0.719 AC XY: 53379 AN XY: 74232

African (AFR) AF: 0.920 AC: 38168 AN: 41470

American (AMR) AF: 0.569 AC: 8663 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2358 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2269 AN: 5148

South Asian (SAS) AF: 0.607 AC: 2921 AN: 4814

European-Finnish (FIN) AF: 0.667 AC: 7023 AN: 10522

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46762 AN: 67946

Other (OTH) AF: 0.722 AC: 1518 AN: 2102

Alfa AF: 0.696 Hom.: 136175

Bravo AF: 0.727

Asia WGS AF: 0.593 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.8
DANN	Benign	0.35
PhyloP100		0.67
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: rs10805347; hg19: chr4-15840839; COSMIC: COSV56888206;