rs12441495

Variant names:

• chr15-40930289-G-A
• rs12441495
• NM_019074.4:c.336+173G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-40930289-G-A
• chr15-40930289-G-C
• chr15-40930289-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019074.4(DLL4):​c.336+173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 690,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DLL4 NM_019074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• aplasia cutis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLL4	NM_019074.4	c.336+173G>A		intron_variant	Intron 2 of 10	ENST00000249749.7	NP_061947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLL4	ENST00000249749.7	c.336+173G>A		intron_variant	Intron 2 of 10	1	NM_019074.4	ENSP00000249749.5
DLL4	ENST00000557876.1	n.838G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 1 AN: 690394 Hom.: 0 Cov.: 9 AF XY: 0.00000284 AC XY: 1 AN XY: 352008

African (AFR) AF: 0.00 AC: 0 AN: 16958

American (AMR) AF: 0.00 AC: 0 AN: 20404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15378

East Asian (EAS) AF: 0.0000310 AC: 1 AN: 32236

South Asian (SAS) AF: 0.00 AC: 0 AN: 51500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 486742

Other (OTH) AF: 0.00 AC: 0 AN: 33866

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.57
PhyloP100		0.30

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

Other links and lift over

dbSNP: rs12441495; hg19: chr15-41222487;