Variant 15-40929564-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.115

Variant links:

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]

DLL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 1416 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLL4	NM_019074.4 link	c.-105C>G		5_prime_UTR_variant	1/11	ENST00000249749.7	NP_061947.1	Q9NR61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLL4	ENST00000249749 link	c.-105C>G		5_prime_UTR_variant	1/11	1	NM_019074.4	ENSP00000249749.5		Q9NR61
DLL4	ENST00000557876.1 link	n.225C>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00928

AC:

1413

AN:

152214

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00504

AC XY:

2284

AN XY:

453232

show subpopulations

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.:

Cov.:

AF XY:

0.00969

AC XY:

722

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.00944

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over