rs11574926

Variant names:

• chr4-15838197-T-C
• rs11574926
• NM_001775.4:c.659+32T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001775.4(CD38):​c.659+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,423,558 control chromosomes in the GnomAD database, including 911 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 0.023 (58 hom., cov: 32)
  • Exomes 𝑓: 0.034 (853 hom.)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• 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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3472/152252) while in subpopulation NFE AF = 0.0352 (2394/68010). AF 95% confidence interval is 0.034. There are 58 homozygotes in GnomAd4. There are 1709 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

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.659+32T>C		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.610+32T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.659+32T>C		intron	N/A	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.*154+32T>C		intron	N/A	ENSP00000427277.1
	CD38	ENST00000510674.1	TSL:5	c.323+32T>C		intron	N/A	ENSP00000423047.1

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3472 AN: 152134 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.00639

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.0252 AC: 6265 AN: 248812 AF XY: 0.0264

Gnomad AFR exome AF: 0.00588

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0446

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0207

Gnomad NFE exome AF: 0.0349

Gnomad OTH exome AF: 0.0240

GnomAD4 exome AF: 0.0335 AC: 42626 AN: 1271306 Hom.: 853 Cov.: 19 AF XY: 0.0338 AC XY: 21709 AN XY: 641868

African (AFR) AF: 0.00495 AC: 147 AN: 29682

American (AMR) AF: 0.0114 AC: 503 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.0420 AC: 1051 AN: 25002

East Asian (EAS) AF: 0.0000773 AC: 3 AN: 38828

South Asian (SAS) AF: 0.0271 AC: 2225 AN: 82034

European-Finnish (FIN) AF: 0.0206 AC: 1097 AN: 53234

Middle Eastern (MID) AF: 0.0157 AC: 85 AN: 5412

European-Non Finnish (NFE) AF: 0.0383 AC: 35969 AN: 938800

Other (OTH) AF: 0.0286 AC: 1546 AN: 54016

GnomAD4 genome AF: 0.0228 AC: 3472 AN: 152252 Hom.: 58 Cov.: 32 AF XY: 0.0230 AC XY: 1709 AN XY: 74446

African (AFR) AF: 0.00638 AC: 265 AN: 41564

American (AMR) AF: 0.0169 AC: 259 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4822

European-Finnish (FIN) AF: 0.0199 AC: 211 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2394 AN: 68010

Other (OTH) AF: 0.0213 AC: 45 AN: 2112

Alfa AF: 0.0308 Hom.: 10

Bravo AF: 0.0211

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.44
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: rs11574926; hg19: chr4-15839820;