4-15778735-G-T

Variant names:

• chr4-15778735-G-T
• rs11574921
• NM_001775.4:c.233+88G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001775.4(CD38):​c.233+88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 790,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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>T		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.320+88G>T		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>T		intron	N/A	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.233+88G>T		intron	N/A	ENSP00000427277.1
	ENSG00000304423	ENST00000803252.1		n.87C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000127 AC: 1 AN: 790048 Hom.: 0 AF XY: 0.00000247 AC XY: 1 AN XY: 405600

African (AFR) AF: 0.00 AC: 0 AN: 19426

American (AMR) AF: 0.00 AC: 0 AN: 26668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17252

East Asian (EAS) AF: 0.00 AC: 0 AN: 33786

South Asian (SAS) AF: 0.00 AC: 0 AN: 62258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3472

European-Non Finnish (NFE) AF: 0.00000181 AC: 1 AN: 551416

Other (OTH) AF: 0.00 AC: 0 AN: 37124

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.51
PhyloP100		0.37
PromoterAI		0.018	Neutral

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;