6-170282969-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005618.4(DLL1):c.2166+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,502 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (5 hom.)
• Consequence: DLL1 NM_005618.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.51

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 6-170282969-G-A is Benign according to our data. Variant chr6-170282969-G-A is described in ClinVar as [Benign]. Clinvar id is 1653252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00163 (249/152318) while in subpopulation AFR AF= 0.00243 (101/41572). AF 95% confidence interval is 0.00205. There are 2 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 249 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL1	NM_005618.4	c.2166+19C>T		intron_variant		ENST00000366756.4
DLL1	XM_005266934.5	c.1569+19C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL1	ENST00000366756.4	c.2166+19C>T		intron_variant		1	NM_005618.4	P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 249 AN: 152200 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00110 AC: 276 AN: 251430 Hom.: 1 AF XY: 0.00108 AC XY: 147 AN XY: 135886

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00181

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.00192 AC: 2802 AN: 1461184 Hom.: 5 Cov.: 34 AF XY: 0.00185 AC XY: 1347 AN XY: 726918

Gnomad4 AFR exome AF: 0.00263

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.000337

Gnomad4 NFE exome AF: 0.00232

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00163 AC: 249 AN: 152318 Hom.: 2 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74482

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00198

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00129 Hom.: 0

Bravo AF: 0.00160

Asia WGS AF: 0.000577 AC: 2 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

Invitae

Jan 21, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.73
Dann	Benign	0.73

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: rs41269631; hg19: chr6-170592057;