6-170283021-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005618.4(DLL1):c.2133C>T(p.Ser711=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,074 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (20 hom.)
• Consequence: DLL1 NM_005618.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.12

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-170283021-G-A is Benign according to our data. Variant chr6-170283021-G-A is described in ClinVar as [Benign]. Clinvar id is 777173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00406 (618/152268) while in subpopulation NFE AF= 0.00513 (349/68016). AF 95% confidence interval is 0.00469. There are 2 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 616 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL1	NM_005618.4	c.2133C>T	p.Ser711=	synonymous_variant	10/11	ENST00000366756.4
DLL1	XM_005266934.5	c.1536C>T	p.Ser512=	synonymous_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL1	ENST00000366756.4	c.2133C>T	p.Ser711=	synonymous_variant	10/11	1	NM_005618.4	P1

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 616 AN: 152150 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00400 AC: 1005 AN: 251342 Hom.: 3 AF XY: 0.00435 AC XY: 591 AN XY: 135830

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00434

Gnomad FIN exome AF: 0.00642

Gnomad NFE exome AF: 0.00457

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00416 AC: 6088 AN: 1461806 Hom.: 20 Cov.: 34 AF XY: 0.00426 AC XY: 3097 AN XY: 727188

Gnomad4 AFR exome AF: 0.00200

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00210

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00452

Gnomad4 FIN exome AF: 0.00705

Gnomad4 NFE exome AF: 0.00424

Gnomad4 OTH exome AF: 0.00437

GnomAD4 genome AF: 0.00406 AC: 618 AN: 152268 Hom.: 2 Cov.: 33 AF XY: 0.00418 AC XY: 311 AN XY: 74450

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.00513

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00379 Hom.: 1

Bravo AF: 0.00368

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00605

EpiControl AF: 0.00646

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	DLL1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.81
Dann	Benign	0.88

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

Other links and lift over

dbSNP: rs118154169; hg19: chr6-170592109;