6-170287611-C-T

Variant names:

• chr6-170287611-C-T
• rs1884190
• NM_005618.4:c.670+628G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005618.4(DLL1):​c.670+628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,256 control chromosomes in the GnomAD database, including 57,608 homozygotes. 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: 𝑓 0.86 (57608 hom., cov: 33)
• Consequence: DLL1 NM_005618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 6 publications found

Genes affected

DLL1 (HGNC:2908): (delta like canonical Notch ligand 1) DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. [provided by RefSeq, Jul 2008]

DLL1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLL1	NM_005618.4	c.670+628G>A		intron_variant	Intron 4 of 10	ENST00000366756.4	NP_005609.3
DLL1	XM_005266934.5	c.670+628G>A		intron_variant	Intron 4 of 10		XP_005266991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLL1	ENST00000366756.4	c.670+628G>A		intron_variant	Intron 4 of 10	1	NM_005618.4	ENSP00000355718.3

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130376 AN: 152138 Hom.: 57588 Cov.: 33

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.875

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.857 AC: 130437 AN: 152256 Hom.: 57608 Cov.: 33 AF XY: 0.862 AC XY: 64144 AN XY: 74452

African (AFR) AF: 0.618 AC: 25657 AN: 41522

American (AMR) AF: 0.926 AC: 14163 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3247 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5064 AN: 5182

South Asian (SAS) AF: 0.944 AC: 4549 AN: 4818

European-Finnish (FIN) AF: 0.973 AC: 10343 AN: 10630

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.947 AC: 64427 AN: 68016

Other (OTH) AF: 0.872 AC: 1841 AN: 2112

Alfa AF: 0.906 Hom.: 110554

Bravo AF: 0.842

Asia WGS AF: 0.904 AC: 3142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1884190; hg19: chr6-170596699;