4-15778735-G-A

Variant names:

• chr4-15778735-G-A
• rs11574921
• NM_001775.4:c.233+88G>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.233+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 941,922 control chromosomes in the GnomAD database, including 2,043 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 (317 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1726 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.0636 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	NM_001775.4	MANE Select	c.233+88G>A		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.320+88G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.233+88G>A		intron	N/A	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.233+88G>A		intron	N/A	ENSP00000427277.1
	ENSG00000304423	ENST00000803252.1		n.87C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9041 AN: 152124 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.0472

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0546

GnomAD4 exome AF: 0.0620 AC: 48940 AN: 789680 Hom.: 1726 AF XY: 0.0612 AC XY: 24797 AN XY: 405446

African (AFR) AF: 0.0490 AC: 951 AN: 19424

American (AMR) AF: 0.0232 AC: 618 AN: 26666

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 594 AN: 17248

East Asian (EAS) AF: 0.0513 AC: 1734 AN: 33784

South Asian (SAS) AF: 0.0496 AC: 3087 AN: 62248

European-Finnish (FIN) AF: 0.133 AC: 5147 AN: 38634

Middle Eastern (MID) AF: 0.0213 AC: 74 AN: 3472

European-Non Finnish (NFE) AF: 0.0628 AC: 34607 AN: 551092

Other (OTH) AF: 0.0573 AC: 2128 AN: 37112

GnomAD4 genome AF: 0.0594 AC: 9047 AN: 152242 Hom.: 317 Cov.: 32 AF XY: 0.0620 AC XY: 4614 AN XY: 74444

African (AFR) AF: 0.0476 AC: 1979 AN: 41568

American (AMR) AF: 0.0302 AC: 462 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3470

East Asian (EAS) AF: 0.0446 AC: 230 AN: 5156

South Asian (SAS) AF: 0.0473 AC: 228 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1436 AN: 10614

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0652 AC: 4433 AN: 67994

Other (OTH) AF: 0.0541 AC: 114 AN: 2108

Alfa AF: 0.0685 Hom.: 58

Bravo AF: 0.0492

Asia WGS AF: 0.0600 AC: 209 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	7.7
DANN	Benign	0.79
PhyloP100		0.37
PromoterAI		0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11574921; hg19: chr4-15780358;