rs17860720

Positions:

• chr6-170282690-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005618.4(DLL1):​c.*184C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 937,340 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0055 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0073 (47 hom.)
• Consequence: DLL1 NM_005618.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.413

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-170282690-G-A is Benign according to our data. Variant chr6-170282690-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1254894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00552 (841/152388) while in subpopulation NFE AF= 0.00775 (527/68038). AF 95% confidence interval is 0.0072. There are 1 homozygotes in gnomad4. There are 414 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 841 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLL1	NM_005618.4	c.*184C>T		3_prime_UTR_variant	11/11	ENST00000366756.4	NP_005609.3
DLL1	XM_005266934.5	c.*184C>T		3_prime_UTR_variant	11/11		XP_005266991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLL1	ENST00000366756	c.*184C>T		3_prime_UTR_variant	11/11	1	NM_005618.4	ENSP00000355718.3

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 842 AN: 152270 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00774

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00729 AC: 5726 AN: 784952 Hom.: 47 Cov.: 11 AF XY: 0.00715 AC XY: 2922 AN XY: 408398

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00507

Gnomad4 ASJ exome AF: 0.00322

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.00413

Gnomad4 FIN exome AF: 0.0154

Gnomad4 NFE exome AF: 0.00798

Gnomad4 OTH exome AF: 0.00825

GnomAD4 genome AF: 0.00552 AC: 841 AN: 152388 Hom.: 1 Cov.: 34 AF XY: 0.00556 AC XY: 414 AN XY: 74516

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00385

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.00775

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00693 Hom.: 0

Bravo AF: 0.00453

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 06, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.87

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: rs17860720; hg19: chr6-170591778;