4-15848936-C-G

Variant names:

• chr4-15848936-C-G
• rs16892463
• ENST00000502843.5:n.*732C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000502843.5(CD38):​n.*732C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 183,888 control chromosomes in the GnomAD database, including 40 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 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (2 hom.)
• Consequence: CD38 ENST00000502843.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 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=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0122 (1862/152278) while in subpopulation AFR AF = 0.0422 (1754/41558). AF 95% confidence interval is 0.0406. There are 38 homozygotes in GnomAd4. There are 860 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502843.5. 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.*334C>G		3_prime_UTR	Exon 8 of 8	NP_001766.2
	CD38	NR_132660.2		n.1188C>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000502843.5	TSL:1	n.*732C>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000427277.1
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.*334C>G		3_prime_UTR	Exon 8 of 8	ENSP00000226279.2
	CD38	ENST00000502843.5	TSL:1	n.*732C>G		3_prime_UTR	Exon 7 of 7	ENSP00000427277.1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1855 AN: 152160 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00228 AC: 72 AN: 31610 Hom.: 2 Cov.: 0 AF XY: 0.00184 AC XY: 30 AN XY: 16274

African (AFR) AF: 0.0433 AC: 53 AN: 1224

American (AMR) AF: 0.00328 AC: 6 AN: 1832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1270

East Asian (EAS) AF: 0.00 AC: 0 AN: 2306

South Asian (SAS) AF: 0.00 AC: 0 AN: 1136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1200

Middle Eastern (MID) AF: 0.00685 AC: 1 AN: 146

European-Non Finnish (NFE) AF: 0.000146 AC: 3 AN: 20528

Other (OTH) AF: 0.00457 AC: 9 AN: 1968

GnomAD4 genome AF: 0.0122 AC: 1862 AN: 152278 Hom.: 38 Cov.: 32 AF XY: 0.0115 AC XY: 860 AN XY: 74460

African (AFR) AF: 0.0422 AC: 1754 AN: 41558

American (AMR) AF: 0.00451 AC: 69 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68018

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00204 Hom.: 2

Bravo AF: 0.0140

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.42
DANN	Benign	0.78
PhyloP100		-1.0
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: rs16892463; hg19: chr4-15850559;