4-15838197-T-C

Position:

• chr4-15838197-T-C

Variant summary

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

The ENST00000226279.8(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 ENST00000226279.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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=-0.85).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.659+32T>C		intron_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.610+32T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.659+32T>C		intron_variant		1	NM_001775.4	ENSP00000226279	P1
CD38	ENST00000502843.5	c.*154+32T>C		intron_variant, NMD_transcript_variant		1		ENSP00000427277
CD38	ENST00000510674.1	c.323+32T>C		intron_variant		5		ENSP00000423047

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

GnomAD3 exomes AF: 0.0252 AC: 6265 AN: 248812 Hom.: 114 AF XY: 0.0264 AC XY: 3552 AN XY: 134518

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 SAS exome AF: 0.0273

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

Gnomad4 AFR exome AF: 0.00495

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.0420

Gnomad4 EAS exome AF: 0.0000773

Gnomad4 SAS exome AF: 0.0271

Gnomad4 FIN exome AF: 0.0206

Gnomad4 NFE exome AF: 0.0383

Gnomad4 OTH exome AF: 0.0286

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

Gnomad4 AFR AF: 0.00638

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0352

Gnomad4 OTH AF: 0.0213

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.69

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: rs11574926; hg19: chr4-15839820;