6-170282835-T-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.*39A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,613,400 control chromosomes in the GnomAD database, including 87,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6328 hom., cov: 34)
  • Exomes 𝑓: 0.33 (80933 hom.)
• Consequence: DLL1 NM_005618.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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=-0.78).
• BP6: Variant 6-170282835-T-G is Benign according to our data. Variant chr6-170282835-T-G is described in ClinVar as [Benign]. Clinvar id is 1267364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL1	NM_005618.4	c.*39A>C		3_prime_UTR_variant	11/11	ENST00000366756.4
DLL1	XM_005266934.5	c.*39A>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL1	ENST00000366756.4	c.*39A>C		3_prime_UTR_variant	11/11	1	NM_005618.4	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42640 AN: 152056 Hom.: 6330 Cov.: 34

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.295

GnomAD3 exomes AF: 0.276 AC: 69476 AN: 251466 Hom.: 10284 AF XY: 0.284 AC XY: 38540 AN XY: 135916

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.265

Gnomad EAS exome AF: 0.222

Gnomad SAS exome AF: 0.259

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.329 AC: 480116 AN: 1461226 Hom.: 80933 Cov.: 36 AF XY: 0.327 AC XY: 237917 AN XY: 726948

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.280 AC: 42641 AN: 152174 Hom.: 6328 Cov.: 34 AF XY: 0.268 AC XY: 19969 AN XY: 74394

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.292

Alfa AF: 0.329 Hom.: 12427

Bravo AF: 0.282

Asia WGS AF: 0.212 AC: 738 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

Apr 12, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.6
Dann	Benign	0.75

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: rs1033583; hg19: chr6-170591923; COSMIC: COSV64537222; COSMIC: COSV64537222;