chr4-15778624-C-T

Variant names:

• chr4-15778624-C-T
• rs78580781
• NM_001775.4:c.210C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001775.4(CD38):​c.210C>T​(p.Tyr70Tyr) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.513
• Publications: 7 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 -17 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 VariationId is 790390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.513 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	NM_001775.4	MANE Select	c.210C>T	p.Tyr70Tyr	synonymous	Exon 1 of 8	NP_001766.2
	CD38	NR_132660.2		n.297C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD38	ENST00000226279.8	TSL:1 MANE Select	c.210C>T	p.Tyr70Tyr	synonymous	Exon 1 of 8	ENSP00000226279.2	P28907-1
	CD38	ENST00000502843.5	TSL:1	n.210C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000427277.1	P28907-2
	CD38	ENST00000868373.1		c.210C>T	p.Tyr70Tyr	synonymous	Exon 1 of 6	ENSP00000538431.1

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

GnomAD2 exomes AF: 0.00318 AC: 795 AN: 250256 AF XY: 0.00334

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 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

African (AFR) AF: 0.000628 AC: 21 AN: 33466

American (AMR) AF: 0.00208 AC: 93 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00640 AC: 167 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86220

European-Finnish (FIN) AF: 0.00175 AC: 93 AN: 53102

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5766

European-Non Finnish (NFE) AF: 0.00486 AC: 5397 AN: 1111150

Other (OTH) AF: 0.00398 AC: 240 AN: 60346

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

African (AFR) AF: 0.00128 AC: 53 AN: 41566

American (AMR) AF: 0.00405 AC: 62 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00507 AC: 345 AN: 68018

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.88
PhyloP100		0.51
PromoterAI		-0.073	Neutral
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: rs78580781; hg19: chr4-15780247;