NM_001775.4:c.233+269C>T

Variant names:

• chr4-15778916-C-T
• rs6834674
• NM_001775.4:c.233+269C>T

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+269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,950 control chromosomes in the GnomAD database, including 6,543 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 0.28 (6543 hom., cov: 32)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD38	NM_001775.4	c.233+269C>T		intron_variant	Intron 1 of 7	ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.320+269C>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.233+269C>T		intron_variant	Intron 1 of 7	1	NM_001775.4	ENSP00000226279.2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43060 AN: 151832 Hom.: 6538 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.284 AC: 43094 AN: 151950 Hom.: 6543 Cov.: 32 AF XY: 0.284 AC XY: 21094 AN XY: 74260

African (AFR) AF: 0.334 AC: 13869 AN: 41480

American (AMR) AF: 0.175 AC: 2675 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 983 AN: 3466

East Asian (EAS) AF: 0.0613 AC: 315 AN: 5140

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4810

European-Finnish (FIN) AF: 0.338 AC: 3577 AN: 10568

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19760 AN: 67890

Other (OTH) AF: 0.261 AC: 551 AN: 2112

Alfa AF: 0.297 Hom.: 2518

Bravo AF: 0.271

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.8
DANN	Benign	0.92
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6834674; hg19: chr4-15780539;