4-15834221-A-C

Variant names:

• chr4-15834221-A-C
• rs1800051
• NM_001775.4:c.504A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001775.4(CD38):​c.504A>C​(p.Ile168Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,596,590 control chromosomes in the GnomAD database, including 2,505 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 0.059 (357 hom., cov: 32)
  • Exomes 𝑓: 0.045 (2148 hom.)
• Consequence: CD38 NM_001775.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 14 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=0.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	NM_001775.4	MANE Select	c.504A>C	p.Ile168Ile	synonymous	Exon 4 of 8	NP_001766.2
	CD38	NR_132660.2		n.455A>C		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.504A>C	p.Ile168Ile	synonymous	Exon 4 of 8	ENSP00000226279.2	P28907-1
	CD38	ENST00000502843.5	TSL:1	n.368A>C		non_coding_transcript_exon	Exon 3 of 7	ENSP00000427277.1	P28907-2
	CD38	ENST00000510674.1	TSL:5	c.168A>C	p.Ile56Ile	synonymous	Exon 3 of 6	ENSP00000423047.1	H0Y950

Frequencies

GnomAD3 genomes AF: 0.0585 AC: 8896 AN: 152136 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0319

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0731

GnomAD2 exomes AF: 0.0620 AC: 15576 AN: 251324 AF XY: 0.0594

Gnomad AFR exome AF: 0.0865

Gnomad AMR exome AF: 0.0889

Gnomad ASJ exome AF: 0.0425

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.0304

Gnomad NFE exome AF: 0.0358

Gnomad OTH exome AF: 0.0551

GnomAD4 exome AF: 0.0447 AC: 64492 AN: 1444336 Hom.: 2148 Cov.: 27 AF XY: 0.0451 AC XY: 32476 AN XY: 719832

African (AFR) AF: 0.0892 AC: 2952 AN: 33094

American (AMR) AF: 0.0843 AC: 3766 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 1072 AN: 26036

East Asian (EAS) AF: 0.160 AC: 6341 AN: 39572

South Asian (SAS) AF: 0.0691 AC: 5936 AN: 85848

European-Finnish (FIN) AF: 0.0304 AC: 1621 AN: 53410

Middle Eastern (MID) AF: 0.0747 AC: 428 AN: 5732

European-Non Finnish (NFE) AF: 0.0356 AC: 38972 AN: 1096158

Other (OTH) AF: 0.0569 AC: 3404 AN: 59792

GnomAD4 genome AF: 0.0585 AC: 8907 AN: 152254 Hom.: 357 Cov.: 32 AF XY: 0.0583 AC XY: 4341 AN XY: 74460

African (AFR) AF: 0.0868 AC: 3607 AN: 41538

American (AMR) AF: 0.0549 AC: 840 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.176 AC: 911 AN: 5168

South Asian (SAS) AF: 0.0814 AC: 393 AN: 4826

European-Finnish (FIN) AF: 0.0319 AC: 338 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0369 AC: 2510 AN: 68016

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0458 Hom.: 842

Bravo AF: 0.0629

Asia WGS AF: 0.141 AC: 490 AN: 3478

EpiCase AF: 0.0405

EpiControl AF: 0.0375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.6
DANN	Benign	0.61
PhyloP100		0.010
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: rs1800051; hg19: chr4-15835844; COSMIC: COSV56890030;