rs6449181

Variant names:

• chr4-15778089-T-C
• rs6449181
• NM_001775.4:c.-326T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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=-0.87).
• 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
CD38	NM_001775.4	c.-326T>C		upstream_gene_variant		ENST00000226279.8	NP_001766.2
CD38	NR_132660.2	n.-239T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD38	ENST00000226279.8	c.-326T>C		upstream_gene_variant		1	NM_001775.4	ENSP00000226279.2
CD38	ENST00000502843.5	n.-326T>C		upstream_gene_variant		1		ENSP00000427277.1
CD38	ENST00000506191.1	n.-209T>C		upstream_gene_variant		2
CD38	ENST00000511430.1	n.-223T>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1680 AN: 152046 Hom.: 20 Cov.: 32

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

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

Other links and lift over

dbSNP: rs6449181; hg19: chr4-15779712;