4-15848707-T-G

Position:

• chr4-15848707-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001775.4(CD38):​c.*105T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 867,486 control chromosomes in the GnomAD database, including 799 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 0.049 (294 hom., cov: 32)
  • Exomes 𝑓: 0.029 (505 hom.)
• Consequence: CD38 NM_001775.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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]

CD38 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.*105T>G		3_prime_UTR_variant	8/8	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.959T>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.*105T>G		3_prime_UTR_variant	8/8	1	NM_001775.4	ENSP00000226279.2
CD38	ENST00000502843.5	n.*503T>G		non_coding_transcript_exon_variant	7/7	1		ENSP00000427277.1
CD38	ENST00000502843.5	n.*503T>G		3_prime_UTR_variant	7/7	1		ENSP00000427277.1

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7476 AN: 152156 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0291 AC: 20784 AN: 715212 Hom.: 505 Cov.: 9 AF XY: 0.0283 AC XY: 10542 AN XY: 372210

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.000259

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0491 AC: 7481 AN: 152274 Hom.: 294 Cov.: 32 AF XY: 0.0475 AC XY: 3537 AN XY: 74450

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0389

Gnomad4 ASJ AF: 0.0567

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0295

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0325 Hom.: 88

Bravo AF: 0.0539

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1803404; hg19: chr4-15850330;