rs41269629

Positions:

• chr6-170282680-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.*194C>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 0.0219 in 812,262 control chromosomes in the GnomAD database, including 473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (83 hom., cov: 34)
  • Exomes 𝑓: 0.022 (390 hom.)
• Consequence: DLL1 NM_005618.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.67

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=-0.62).
• BP6: Variant 6-170282680-G-A is Benign according to our data. Variant chr6-170282680-G-A is described in ClinVar as [Benign]. Clinvar id is 1268928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0198 (3024/152368) while in subpopulation NFE AF= 0.0224 (1524/68032). AF 95% confidence interval is 0.0215. There are 83 homozygotes in gnomad4. There are 1739 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3024 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLL1	NM_005618.4	c.*194C>T		3_prime_UTR_variant	11/11	ENST00000366756.4	NP_005609.3
DLL1	XM_005266934.5	c.*194C>T		3_prime_UTR_variant	11/11		XP_005266991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLL1	ENST00000366756.4	c.*194C>T		3_prime_UTR_variant	11/11	1	NM_005618.4	ENSP00000355718	P1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3022 AN: 152250 Hom.: 83 Cov.: 34

Gnomad AFR AF: 0.00366

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0223 AC: 14746 AN: 659894 Hom.: 390 Cov.: 9 AF XY: 0.0215 AC XY: 7475 AN XY: 348426

Gnomad4 AFR exome AF: 0.00368

Gnomad4 AMR exome AF: 0.00536

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.00361

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0210

Gnomad4 OTH exome AF: 0.0200

GnomAD4 genome AF: 0.0198 AC: 3024 AN: 152368 Hom.: 83 Cov.: 34 AF XY: 0.0233 AC XY: 1739 AN XY: 74502

Gnomad4 AFR AF: 0.00368

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0263 Hom.: 8

Bravo AF: 0.0108

Asia WGS AF: 0.00173 AC: 6 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

Jun 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.1
DANN	Benign	0.81

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: rs41269629; hg19: chr6-170591768;