4-15840187-A-G

Variant names:

• chr4-15840187-A-G
• rs11574929
• NM_001775.4:c.752+69A>G

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.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
• Publications: 2 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=-0.91).
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 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.752+69A>G		intron	N/A	NP_001766.2
	CD38	NR_132660.2		n.703+69A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.752+69A>G		intron	N/A	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.*247+69A>G		intron	N/A	ENSP00000427277.1
	CD38	ENST00000510674.1	TSL:5	c.416+69A>G		intron	N/A	ENSP00000423047.1

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

African (AFR) AF: 0.00623 AC: 145 AN: 23286

American (AMR) AF: 0.0104 AC: 448 AN: 42916

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 378 AN: 22776

East Asian (EAS) AF: 0.000134 AC: 5 AN: 37438

South Asian (SAS) AF: 0.0213 AC: 1600 AN: 75078

European-Finnish (FIN) AF: 0.0183 AC: 971 AN: 53114

Middle Eastern (MID) AF: 0.0451 AC: 214 AN: 4742

European-Non Finnish (NFE) AF: 0.0291 AC: 18905 AN: 649844

Other (OTH) AF: 0.0234 AC: 1019 AN: 43508

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

African (AFR) AF: 0.00556 AC: 231 AN: 41564

American (AMR) AF: 0.0131 AC: 200 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4824

European-Finnish (FIN) AF: 0.0195 AC: 207 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0276 AC: 1881 AN: 68036

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0243 Hom.: 24

Bravo AF: 0.0169

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.56
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism

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: rs11574929; hg19: chr4-15841810;