rs6449197

Positions:

• chr4-15813299-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001775.4(CD38):​c.234-3212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,848 control chromosomes in the GnomAD database, including 5,723 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 0.22 (5723 hom., cov: 32)
• Consequence: CD38 NM_001775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD38	NM_001775.4	c.234-3212C>T		intron_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.321-3212C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.234-3212C>T		intron_variant		1	NM_001775.4	ENSP00000226279	P1
CD38	ENST00000502843.5	c.234-3212C>T		intron_variant, NMD_transcript_variant		1		ENSP00000427277
CD38	ENST00000506191.1	n.351-3212C>T		intron_variant, non_coding_transcript_variant		2
CD38	ENST00000511430.1	n.337-3212C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34020 AN: 151730 Hom.: 5702 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.224 AC: 34087 AN: 151848 Hom.: 5723 Cov.: 32 AF XY: 0.223 AC XY: 16552 AN XY: 74200

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.213

Alfa AF: 0.151 Hom.: 1029

Bravo AF: 0.232

Asia WGS AF: 0.230 AC: 798 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.15

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: rs6449197; hg19: chr4-15814922;