4-100187718-GTT-GT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_145244.4(DDIT4L):c.540del(p.Lys180AsnfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 1,609,404 control chromosomes in the GnomAD database, including 7,227 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (528 hom., cov: 31)
  • Exomes 𝑓: 0.091 (6699 hom.)
• Consequence: DDIT4L NM_145244.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

Genes affected

DDIT4L (HGNC:30555): (DNA damage inducible transcript 4 like) Predicted to be involved in negative regulation of signal transduction. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

H2AZ1-DT (HGNC:40271): (H2AZ1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDIT4L	NM_145244.4	c.540del	p.Lys180AsnfsTer5	frameshift_variant	3/3	ENST00000273990.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDIT4L	ENST00000273990.6	c.540del	p.Lys180AsnfsTer5	frameshift_variant	3/3	1	NM_145244.4	P1
H2AZ1-DT	ENST00000515026.1	n.730-7341del		intron_variant, non_coding_transcript_variant		5
DDIT4L	ENST00000502763.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12483 AN: 152038 Hom.: 529 Cov.: 31

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0967

GnomAD3 exomes AF: 0.0776 AC: 19145 AN: 246778 Hom.: 957 AF XY: 0.0829 AC XY: 11062 AN XY: 133396

Gnomad AFR exome AF: 0.0794

Gnomad AMR exome AF: 0.0436

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.000553

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.0582

Gnomad NFE exome AF: 0.0903

Gnomad OTH exome AF: 0.0865

GnomAD4 exome AF: 0.0912 AC: 132963 AN: 1457248 Hom.: 6699 Cov.: 29 AF XY: 0.0931 AC XY: 67478 AN XY: 724750

Gnomad4 AFR exome AF: 0.0786

Gnomad4 AMR exome AF: 0.0464

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0597

Gnomad4 NFE exome AF: 0.0954

Gnomad4 OTH exome AF: 0.0917

GnomAD4 genome AF: 0.0821 AC: 12490 AN: 152156 Hom.: 528 Cov.: 31 AF XY: 0.0813 AC XY: 6045 AN XY: 74394

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.0953

Alfa AF: 0.0902 Hom.: 120

Bravo AF: 0.0807

Asia WGS AF: 0.0440 AC: 152 AN: 3478

EpiCase AF: 0.0975

EpiControl AF: 0.0949

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs58706659; hg19: chr4-101108875;