15-40929564-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_019074.4(DLL4):c.-105C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,061,306 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (49 hom.)
• Consequence: DLL4 NM_019074.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115

Genes affected

DLL4 (HGNC:2910): (delta like canonical Notch ligand 4) This gene is a homolog of the Drosophila delta gene. The delta gene family encodes Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-40929564-C-G is Benign according to our data. Variant chr15-40929564-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1193817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0093 (1416/152332) while in subpopulation AFR AF= 0.0253 (1053/41566). AF 95% confidence interval is 0.0241. There are 20 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1413 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL4	NM_019074.4	c.-105C>G		5_prime_UTR_variant	1/11	ENST00000249749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL4	ENST00000249749.7	c.-105C>G		5_prime_UTR_variant	1/11	1	NM_019074.4	P1
DLL4	ENST00000557876.1	n.225C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.00928 AC: 1413 AN: 152214 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.00909

GnomAD4 exome AF: 0.00422 AC: 3840 AN: 908974 Hom.: 49 Cov.: 12 AF XY: 0.00504 AC XY: 2284 AN XY: 453232

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.00299

Gnomad4 ASJ exome AF: 0.00587

Gnomad4 EAS exome AF: 0.0000308

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.000163

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.00651

GnomAD4 genome AF: 0.00930 AC: 1416 AN: 152332 Hom.: 20 Cov.: 33 AF XY: 0.00969 AC XY: 722 AN XY: 74486

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.00944

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.67

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: rs111494897; hg19: chr15-41221762;