rs6449181

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001775.4(CD38):​c.-326T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 152,164 control chromosomes in the GnomAD database, including 20 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 0.011 ( 20 hom., cov: 32)

Consequence

CD38
NM_001775.4 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.527
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (1681/152164) while in subpopulation NFE AF= 0.0173 (1174/67996). AF 95% confidence interval is 0.0164. There are 20 homozygotes in gnomad4. There are 792 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD38NM_001775.4 linkc.-326T>C upstream_gene_variant ENST00000226279.8 NP_001766.2 P28907-1B4E006
CD38NR_132660.2 linkn.-239T>C upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD38ENST00000226279.8 linkc.-326T>C upstream_gene_variant 1 NM_001775.4 ENSP00000226279.2 P28907-1
CD38ENST00000502843.5 linkn.-326T>C upstream_gene_variant 1 ENSP00000427277.1 P28907-2
CD38ENST00000506191.1 linkn.-209T>C upstream_gene_variant 2
CD38ENST00000511430.1 linkn.-223T>C upstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0110
AC:
1680
AN:
152046
Hom.:
20
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00290
Gnomad AMI
AF:
0.00987
Gnomad AMR
AF:
0.00969
Gnomad ASJ
AF:
0.00375
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.0177
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0173
Gnomad OTH
AF:
0.0124
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0110
AC:
1681
AN:
152164
Hom.:
20
Cov.:
32
AF XY:
0.0106
AC XY:
792
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00289
Gnomad4 AMR
AF:
0.00968
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.0177
Gnomad4 NFE
AF:
0.0173
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.0153
Hom.:
28
Bravo
AF:
0.00989
Asia WGS
AF:
0.00144
AC:
6
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
1.8
DANN
Benign
0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6449181; hg19: chr4-15779712; API