4-100187718-GTT-GT

Variant names:

• chr4-100187718-GT-G
• rs58706659
• NM_145244.4:c.540delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_145244.4(DDIT4L):​c.540delA​(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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145244.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDIT4L	NM_145244.4	MANE Select	c.540delA	p.Lys180AsnfsTer5	frameshift	Exon 3 of 3	NP_660287.1	Q96D03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDIT4L	ENST00000273990.6	TSL:1 MANE Select	c.540delA	p.Lys180AsnfsTer5	frameshift	Exon 3 of 3	ENSP00000354830.2	Q96D03
	DDIT4L	ENST00000966423.1		c.540delA	p.Lys180AsnfsTer5	frameshift	Exon 3 of 3	ENSP00000636482.1
	H2AZ1-DT	ENST00000515026.1	TSL:5	n.730-7341delT		intron	N/A

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

GnomAD2 exomes AF: 0.0776 AC: 19145 AN: 246778 AF XY: 0.0829

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 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

African (AFR) AF: 0.0786 AC: 2595 AN: 33030

American (AMR) AF: 0.0464 AC: 2012 AN: 43396

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2800 AN: 26038

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39688

South Asian (SAS) AF: 0.119 AC: 10129 AN: 84934

European-Finnish (FIN) AF: 0.0597 AC: 3185 AN: 53386

Middle Eastern (MID) AF: 0.127 AC: 734 AN: 5758

European-Non Finnish (NFE) AF: 0.0954 AC: 105969 AN: 1110800

Other (OTH) AF: 0.0917 AC: 5522 AN: 60218

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

African (AFR) AF: 0.0808 AC: 3353 AN: 41500

American (AMR) AF: 0.0668 AC: 1021 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.112 AC: 540 AN: 4826

European-Finnish (FIN) AF: 0.0646 AC: 684 AN: 10588

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0916 AC: 6230 AN: 67994

Other (OTH) AF: 0.0953 AC: 201 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53
Mutation Taster		=134/66	polymorphism (auto)

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

Other links and lift over

dbSNP: rs58706659; hg19: chr4-101108875; COSMIC: COSV56766929; COSMIC: COSV56766929;