6-170282932-C-G

Variant summary

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

The NM_005618.4(DLL1):c.2167-53G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,614,166 control chromosomes in the GnomAD database, including 1,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (625 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (512 hom.)
• Consequence: DLL1 NM_005618.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.694

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-170282932-C-G is Benign according to our data. Variant chr6-170282932-C-G is described in ClinVar as [Benign]. Clinvar id is 1269335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL1	NM_005618.4	c.2167-53G>C		intron_variant		ENST00000366756.4
DLL1	XM_005266934.5	c.1570-53G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL1	ENST00000366756.4	c.2167-53G>C		intron_variant		1	NM_005618.4	P1

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7404 AN: 152178 Hom.: 622 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.00516 AC: 7543 AN: 1461870 Hom.: 512 Cov.: 34 AF XY: 0.00449 AC XY: 3265 AN XY: 727236

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000487

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0488 AC: 7431 AN: 152296 Hom.: 625 Cov.: 33 AF XY: 0.0475 AC XY: 3534 AN XY: 74468

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0187

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.00768 Hom.: 5

Bravo AF: 0.0564

Asia WGS AF: 0.00664 AC: 23 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

Dec 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.069
Dann	Benign	0.42

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: rs1546951; hg19: chr6-170592020;