4-15778624-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001775.4(CD38):c.210C>T(p.Tyr70=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,612,850 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (23 hom.)
• Consequence: CD38 NM_001775.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.513

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-15778624-C-T is Benign according to our data. Variant chr4-15778624-C-T is described in ClinVar as [Benign]. Clinvar id is 790390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.513 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD38	NM_001775.4	c.210C>T	p.Tyr70=	synonymous_variant	1/8	ENST00000226279.8
CD38	NR_132660.2	n.297C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD38	ENST00000226279.8	c.210C>T	p.Tyr70=	synonymous_variant	1/8	1	NM_001775.4	P1
CD38	ENST00000502843.5	c.210C>T	p.Tyr70=	synonymous_variant, NMD_transcript_variant	1/7	1
CD38	ENST00000506191.1	n.327C>T		non_coding_transcript_exon_variant	1/2	2
CD38	ENST00000511430.1	n.313C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 503 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00318 AC: 795 AN: 250256 Hom.: 3 AF XY: 0.00334 AC XY: 452 AN XY: 135326

Gnomad AFR exome AF: 0.000988

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00686

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00201

Gnomad NFE exome AF: 0.00496

Gnomad OTH exome AF: 0.00475

GnomAD4 exome AF: 0.00416 AC: 6069 AN: 1460568 Hom.: 23 Cov.: 31 AF XY: 0.00406 AC XY: 2953 AN XY: 726592

Gnomad4 AFR exome AF: 0.000628

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00640

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.00175

Gnomad4 NFE exome AF: 0.00486

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.00331 AC: 504 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74456

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00507

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00441 Hom.: 0

Bravo AF: 0.00337

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00534

EpiControl AF: 0.00504

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.3
Dann	Benign	0.88

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: rs78580781; hg19: chr4-15780247;