Variant 19-39500597-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_StrongBA1

The NM_203486.3(DLL3):c.352-18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,605,918 control chromosomes in the GnomAD database, including 84,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6497 hom., cov: 30)

Exomes 𝑓: 0.32 ( 78103 hom. )

Consequence

DLL3
NM_203486.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0640

Variant links:

Genes affected

DLL3 (HGNC:2909): (delta like canonical Notch ligand 3) This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. Mutations in this gene cause autosomal recessive spondylocostal dysostosis 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DLL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 19-39500597-C-G is Benign according to our data. Variant chr19-39500597-C-G is described in ClinVar as [Benign]. Clinvar id is 260778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-39500597-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLL3	NM_203486.3 linkuse as main transcript	c.352-18C>G		intron_variant		ENST00000356433.10	NP_982353.1
DLL3	NM_016941.4 linkuse as main transcript	c.352-18C>G		intron_variant			NP_058637.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DLL3	ENST00000356433.10 linkuse as main transcript	c.352-18C>G	intron_variant	2	NM_203486.3	ENSP00000348810	P1	Q9NYJ7-2
DLL3	ENST00000205143.4 linkuse as main transcript	c.352-18C>G	intron_variant	1		ENSP00000205143		Q9NYJ7-1
DLL3	ENST00000600437.1 linkuse as main transcript	n.432-18C>G	intron_variant, non_coding_transcript_variant	1
DLL3	ENST00000596614.5 linkuse as main transcript	c.352-18C>G	intron_variant	2		ENSP00000471688

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42855

AN:

151854

Hom.:

6498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.307

AC:

77079

AN:

251454

Hom.:

12403

AF XY:

0.313

AC XY:

42546

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.323

AC:

469227

AN:

1453946

Hom.:

78103

Cov.:

AF XY:

0.325

AC XY:

234910

AN XY:

723654

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.282

AC:

42855

AN:

151972

Hom.:

6497

Cov.:

AF XY:

0.286

AC XY:

21250

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.252

Hom.:

962

Bravo

AF:

0.267

Asia WGS

AF:

0.227

AC:

790

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Spondylocostal dysostosis 1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.4

DANN

Benign

0.78

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