Genetic Variant ENST00000454686.1:n.575C>T (chr6-36674391-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000454686.1(LAP3P2):n.575C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,447,710 control chromosomes in the GnomAD database, including 24,138 homozygotes. 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 0.22 ( 4416 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19722 hom. )

Consequence

LAP3P2
ENST00000454686.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

2 publications found

Variant links:

COSMIC-nc: COSV55191162

Genes affected

LAP3P2 (HGNC:42365): (leucine aminopeptidase 3 pseudogene 2)

LAP3P2 links:

PANDAR (HGNC:44048): (promoter of CDKN1A antisense DNA damage activated RNA) This gene produces a non-coding RNA that is thought to regulate the response to DNA damage. This gene is induced by tumor protein p53 and interacts with and modulates the activity of a transcription factor that induce pro-apoptotic genes. Deregulation of this gene is associated with cancer progression. [provided by RefSeq, Dec 2017]

PANDAR links:

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new If you want to explore the variant's impact on the transcript ENST00000454686.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454686.1. 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
	PANDAR	NR_109836.1		n.736G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAP3P2	ENST00000454686.1	TSL:6	n.575C>T		non_coding_transcript_exon	Exon 1 of 1
	PANDAR	ENST00000629595.1	TSL:6	n.736G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32973

AN:

151904

Hom.:

4401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.0957

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.219

GnomAD4 exome

AF:

0.151

AC:

195207

AN:

1295688

Hom.:

19722

Cov.:

AF XY:

0.148

AC XY:

96523

AN XY:

652434

show subpopulations

African (AFR)

AF:

0.315

AC:

9215

AN:

29244

American (AMR)

AF:

0.411

AC:

17731

AN:

43128

Ashkenazi Jewish (ASJ)

AF:

0.0902

AC:

2250

AN:

24940

East Asian (EAS)

AF:

0.468

AC:

18052

AN:

38566

South Asian (SAS)

AF:

0.109

AC:

9039

AN:

82694

European-Finnish (FIN)

AF:

0.111

AC:

5909

AN:

53100

Middle Eastern (MID)

AF:

0.171

AC:

902

AN:

5286

European-Non Finnish (NFE)

AF:

0.128

AC:

123546

AN:

964214

Other (OTH)

AF:

0.157

AC:

8563

AN:

54516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

6981

13961

20942

27922

34903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4366

8732

13098

17464

21830

<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:

0.217

AC:

33032

AN:

152022

Hom.:

4416

Cov.:

AF XY:

0.218

AC XY:

16197

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.325

AC:

13485

AN:

41440

American (AMR)

AF:

0.323

AC:

4930

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0957

AC:

332

AN:

3470

East Asian (EAS)

AF:

0.421

AC:

2171

AN:

5154

South Asian (SAS)

AF:

0.122

AC:

590

AN:

4822

European-Finnish (FIN)

AF:

0.118

AC:

1249

AN:

10578

Middle Eastern (MID)

AF:

0.158

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.142

AC:

9638

AN:

67968

Other (OTH)

AF:

0.219

AC:

462

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1213

2426

3640

4853

6066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.188

Hom.:

457

Bravo

AF:

0.245

Asia WGS

AF:

0.252

AC:

875

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.4

(source)

DANN

Benign

0.88

PhyloP100

-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over