rs12644506

Positions:

• chr4-15798255-C-T

Variant summary

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

The NM_001775.4(CD38):​c.234-18256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,184 control chromosomes in the GnomAD database, including 277 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 0.053 (277 hom., cov: 32)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.234-18256C>T		intron_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.321-18256C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.234-18256C>T		intron_variant		1	NM_001775.4	ENSP00000226279	P1
CD38	ENST00000502843.5	c.234-18256C>T		intron_variant, NMD_transcript_variant		1		ENSP00000427277
CD38	ENST00000506191.1	n.351-18256C>T		intron_variant, non_coding_transcript_variant		2
CD38	ENST00000511430.1	n.337-18256C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8011 AN: 152066 Hom.: 277 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0527 AC: 8014 AN: 152184 Hom.: 277 Cov.: 32 AF XY: 0.0553 AC XY: 4114 AN XY: 74400

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.0457

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0582 Hom.: 82

Bravo AF: 0.0413

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.67
DANN	Benign	0.62

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: rs12644506; hg19: chr4-15799878;