4-15849062-C-T

Variant names:

• chr4-15849062-C-T
• rs1130169
• NM_001775.4:c.*460C>T

Variant summary

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

The NM_001775.4(CD38):​c.*460C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 153,622 control chromosomes in the GnomAD database, including 19,300 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 0.50 (19114 hom., cov: 31)
  • Exomes 𝑓: 0.44 (186 hom.)
• Consequence: CD38 NM_001775.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.*460C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.1314C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.*460C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001775.4	ENSP00000226279.2
CD38	ENST00000502843.5	n.*858C>T		non_coding_transcript_exon_variant	Exon 7 of 7	1		ENSP00000427277.1
CD38	ENST00000502843.5	n.*858C>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000427277.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75434 AN: 151796 Hom.: 19085 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.444 AC: 758 AN: 1708 Hom.: 186 Cov.: 0 AF XY: 0.446 AC XY: 382 AN XY: 856

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.235

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.497 AC: 75507 AN: 151914 Hom.: 19114 Cov.: 31 AF XY: 0.496 AC XY: 36800 AN XY: 74250

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.487

Alfa AF: 0.489 Hom.: 23720

Bravo AF: 0.485

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs1130169; hg19: chr4-15850685;