rs12441495

Positions:

• chr15-40930289-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019074.4(DLL4):​c.336+173G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 841,496 control chromosomes in the GnomAD database, including 5,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (671 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4669 hom.)
• Consequence: DLL4 NM_019074.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.296

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=-0.67).
• BP6: Variant 15-40930289-G-C is Benign according to our data. Variant chr15-40930289-G-C is described in ClinVar as [Benign]. Clinvar id is 1290722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL4	NM_019074.4	c.336+173G>C		intron_variant		ENST00000249749.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL4	ENST00000249749.7	c.336+173G>C		intron_variant		1	NM_019074.4	P1
DLL4	ENST00000557876.1	n.838G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 12355 AN: 151470 Hom.: 670 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0916

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0909

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0964

GnomAD4 exome AF: 0.108 AC: 74596 AN: 689906 Hom.: 4669 Cov.: 9 AF XY: 0.107 AC XY: 37467 AN XY: 351774

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0733

Gnomad4 ASJ exome AF: 0.0878

Gnomad4 EAS exome AF: 0.000279

Gnomad4 SAS exome AF: 0.0566

Gnomad4 FIN exome AF: 0.0791

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0815 AC: 12354 AN: 151590 Hom.: 671 Cov.: 32 AF XY: 0.0783 AC XY: 5797 AN XY: 74032

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.0909

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.0527

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0950

Alfa AF: 0.0926 Hom.: 91

Bravo AF: 0.0801

Asia WGS AF: 0.0200 AC: 71 AN: 3478

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

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.51

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: rs12441495; hg19: chr15-41222487;