rs3796868

Variant names:

• chr4-15816768-G-A
• rs3796868
• NM_001775.4:c.363+128G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-15816768-G-A
• chr4-15816768-G-C

Variant summary

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

The NM_001775.4(CD38):​c.363+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,010,576 control chromosomes in the GnomAD database, including 14,954 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 0.14 (1703 hom., cov: 32)
  • Exomes 𝑓: 0.17 (13251 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.363+128G>A		intron_variant	Intron 2 of 7	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.450+128G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.363+128G>A		intron_variant	Intron 2 of 7	1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21284 AN: 152050 Hom.: 1705 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.173 AC: 37890 AN: 219068 AF XY: 0.178

Gnomad AFR exome AF: 0.0654

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.170 AC: 146183 AN: 858408 Hom.: 13251 Cov.: 11 AF XY: 0.175 AC XY: 78612 AN XY: 450428

African (AFR) AF: 0.0681 AC: 1447 AN: 21244

American (AMR) AF: 0.161 AC: 6618 AN: 41114

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 2983 AN: 21260

East Asian (EAS) AF: 0.160 AC: 5559 AN: 34744

South Asian (SAS) AF: 0.253 AC: 18168 AN: 71756

European-Finnish (FIN) AF: 0.178 AC: 8712 AN: 48980

Middle Eastern (MID) AF: 0.222 AC: 1009 AN: 4546

European-Non Finnish (NFE) AF: 0.165 AC: 95013 AN: 575222

Other (OTH) AF: 0.169 AC: 6674 AN: 39542

GnomAD4 genome AF: 0.140 AC: 21282 AN: 152168 Hom.: 1703 Cov.: 32 AF XY: 0.142 AC XY: 10557 AN XY: 74394

African (AFR) AF: 0.0661 AC: 2743 AN: 41526

American (AMR) AF: 0.146 AC: 2235 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.155 AC: 803 AN: 5170

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4818

European-Finnish (FIN) AF: 0.180 AC: 1908 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11482 AN: 67990

Other (OTH) AF: 0.153 AC: 323 AN: 2108

Alfa AF: 0.157 Hom.: 5233

Bravo AF: 0.133

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-0.78
PromoterAI		-0.015	Neutral
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: rs3796868; hg19: chr4-15818391;