dbSNP rs56763427: DDIT4L:p.Lys180Lys (chr4-100187719-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_145244.4(DDIT4L):c.540A>G(p.Lys180Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,332,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

DDIT4L
NM_145244.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.529

Publications

1 publications found

Variant links:

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]

DDIT4L links:

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

H2AZ1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=0.529 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDIT4L	NM_145244.4 link	c.540A>G	p.Lys180Lys	synonymous_variant	Exon 3 of 3	ENST00000273990.6	NP_660287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DDIT4L	ENST00000273990.6 link	c.540A>G	p.Lys180Lys	synonymous_variant	Exon 3 of 3	1	NM_145244.4	ENSP00000354830.2
H2AZ1-DT	ENST00000515026.1 link	n.730-7346T>C		intron_variant	Intron 5 of 5	5
DDIT4L	ENST00000502763.1 link	c.*9A>G		downstream_gene_variant		2		ENSP00000427301.1
DDIT4L	ENST00000513992.1 link	c.*156A>G		downstream_gene_variant		4		ENSP00000427040.1

Frequencies

GnomAD3 genomes

AF:

0.0000156

AC:

AN:

128140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000811

AC:

AN:

246756

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000664

AC:

AN:

1204630

Hom.:

Cov.:

AF XY:

0.00000503

AC XY:

AN XY:

596828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28046

American (AMR)

AF:

0.0000507

AC:

AN:

39448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20726

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

66172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4416

European-Non Finnish (NFE)

AF:

0.00000660

AC:

AN:

909158

Other (OTH)

AF:

0.00

AC:

AN:

49774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000156

AC:

AN:

128140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34954

American (AMR)

AF:

0.000150

AC:

AN:

13306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2754

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

3826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56084

Other (OTH)

AF:

0.00

AC:

AN:

1704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000305

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.7

(source)

DANN

Benign

0.71

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over