rs11574930

Variant names:

• chr4-15840268-C-A
• rs11574930
• NM_001775.4:c.752+150C>A

Variant summary

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

The NM_001775.4(CD38):​c.752+150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 729,280 control chromosomes in the GnomAD database, including 678 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 0.045 (487 hom., cov: 31)
  • Exomes 𝑓: 0.0069 (191 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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.752+150C>A		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.703+150C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.752+150C>A		intron	N/A	ENSP00000226279.2	P28907-1
	CD38	ENST00000502843.5	TSL:1	n.*247+150C>A		intron	N/A	ENSP00000427277.1	P28907-2
	CD38	ENST00000868373.1		c.530+150C>A		intron	N/A	ENSP00000538431.1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6819 AN: 152098 Hom.: 486 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.0307

GnomAD4 exome AF: 0.00692 AC: 3996 AN: 577064 Hom.: 191 AF XY: 0.00629 AC XY: 1933 AN XY: 307378

African (AFR) AF: 0.146 AC: 2194 AN: 15006

American (AMR) AF: 0.0148 AC: 390 AN: 26296

Ashkenazi Jewish (ASJ) AF: 0.00355 AC: 57 AN: 16046

East Asian (EAS) AF: 0.0000292 AC: 1 AN: 34266

South Asian (SAS) AF: 0.00468 AC: 254 AN: 54272

European-Finnish (FIN) AF: 0.0000837 AC: 4 AN: 47796

Middle Eastern (MID) AF: 0.0236 AC: 90 AN: 3816

European-Non Finnish (NFE) AF: 0.00161 AC: 562 AN: 348980

Other (OTH) AF: 0.0145 AC: 444 AN: 30586

GnomAD4 genome AF: 0.0449 AC: 6842 AN: 152216 Hom.: 487 Cov.: 31 AF XY: 0.0437 AC XY: 3249 AN XY: 74428

African (AFR) AF: 0.152 AC: 6301 AN: 41498

American (AMR) AF: 0.0202 AC: 309 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00168 AC: 114 AN: 68022

Other (OTH) AF: 0.0304 AC: 64 AN: 2106

Alfa AF: 0.0339 Hom.: 57

Bravo AF: 0.0508

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.28
PhyloP100		0.58
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: rs11574930; hg19: chr4-15841891;