rs11574929

chr4-15840187-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001775.4(CD38):c.752+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,105,020 control chromosomes in the GnomAD database, including 381 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 0.018 (34 hom., cov: 31)
  • Exomes 𝑓: 0.025 (347 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0178 (2705/152318) while in subpopulation NFE AF= 0.0276 (1881/68036). AF 95% confidence interval is 0.0266. There are 34 homozygotes in gnomad4. There are 1295 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD38	NM_001775.4	c.752+69A>G		intron_variant		ENST00000226279.8
CD38	NR_132660.2	n.703+69A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD38	ENST00000226279.8	c.752+69A>G		intron_variant		1	NM_001775.4	P1
CD38	ENST00000502843.5	c.*247+69A>G		intron_variant, NMD_transcript_variant		1
CD38	ENST00000510674.1	c.416+69A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2708 AN: 152200 Hom.: 34 Cov.: 31

Gnomad AFR AF: 0.00557

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0249 AC: 23685 AN: 952702 Hom.: 347 AF XY: 0.0248 AC XY: 12260 AN XY: 494982

Gnomad4 AFR exome AF: 0.00623

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.000134

Gnomad4 SAS exome AF: 0.0213

Gnomad4 FIN exome AF: 0.0183

Gnomad4 NFE exome AF: 0.0291

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0178 AC: 2705 AN: 152318 Hom.: 34 Cov.: 31 AF XY: 0.0174 AC XY: 1295 AN XY: 74484

Gnomad4 AFR AF: 0.00556

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0195

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0230 Hom.: 11

Bravo AF: 0.0169

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.15
Dann	Benign	0.56

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: rs11574929; hg19: chr4-15841810;