4-15848363-G-T

Variant names:

• chr4-15848363-G-T
• rs3796863
• NM_001775.4:c.840-176G>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.840-176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,818 control chromosomes in the GnomAD database, including 14,124 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 0.40 (14124 hom., cov: 30)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 81 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 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.840-176G>T		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.791-176G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.840-176G>T		intron	N/A	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.*335-176G>T		intron	N/A	ENSP00000427277.1
	ENSG00000304423	ENST00000803248.1		n.198+21768C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60987 AN: 151700 Hom.: 14101 Cov.: 30

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.402 AC: 61064 AN: 151818 Hom.: 14124 Cov.: 30 AF XY: 0.400 AC XY: 29704 AN XY: 74198

African (AFR) AF: 0.645 AC: 26670 AN: 41348

American (AMR) AF: 0.313 AC: 4775 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3466

East Asian (EAS) AF: 0.339 AC: 1747 AN: 5160

South Asian (SAS) AF: 0.365 AC: 1749 AN: 4798

European-Finnish (FIN) AF: 0.355 AC: 3735 AN: 10530

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20349 AN: 67936

Other (OTH) AF: 0.403 AC: 848 AN: 2106

Alfa AF: 0.330 Hom.: 7543

Bravo AF: 0.409

Asia WGS AF: 0.410 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.61
PhyloP100		-0.57
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: rs3796863; hg19: chr4-15849986;