Variant 19-39502775-C-T 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.410-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,333,112 control chromosomes in the GnomAD database, including 70,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6487 hom., cov: 32)

Exomes 𝑓: 0.32 ( 63932 hom. )

Consequence

DLL3
NM_203486.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.100

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:

DLL3 (HGNC:):

DLL3 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=-0.77).

BP6

Variant 19-39502775-C-T is Benign according to our data. Variant chr19-39502775-C-T is described in ClinVar as [Benign]. Clinvar id is 260779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.410-40C>T		intron_variant		ENST00000356433.10	NP_982353.1	Q9NYJ7-2
DLL3	NM_016941.4 linkuse as main transcript	c.410-40C>T		intron_variant			NP_058637.1	Q9NYJ7-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DLL3	ENST00000356433.10 linkuse as main transcript	c.410-40C>T	intron_variant	2	NM_203486.3	ENSP00000348810.4	Q9NYJ7-2
DLL3	ENST00000205143.4 linkuse as main transcript	c.410-40C>T	intron_variant	1		ENSP00000205143.3	Q9NYJ7-1
DLL3	ENST00000600437.1 linkuse as main transcript	n.490-40C>T	intron_variant	1
DLL3	ENST00000596614.5 linkuse as main transcript	c.409+2103C>T	intron_variant	2		ENSP00000471688.1	M0R177

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42780

AN:

151924

Hom.:

6488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.294

AC:

12762

AN:

43468

Hom.:

2041

AF XY:

0.305

AC XY:

7735

AN XY:

25332

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.0908

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.325

AC:

383487

AN:

1181072

Hom.:

63932

Cov.:

AF XY:

0.327

AC XY:

187066

AN XY:

572138

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.281

AC:

42780

AN:

152040

Hom.:

6487

Cov.:

AF XY:

0.285

AC XY:

21223

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.314

Hom.:

981

Bravo

AF:

0.267

Asia WGS

AF:

0.227

AC:

789

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Spondylocostal dysostosis 1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.8

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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