ENST00000454686.1:n.593T>G

Variant names:

• chr6-36674409-T-G
• rs4714002
• ENST00000454686.1:n.593T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000454686.1(LAP3P2):​n.593T>G 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 0.157 in 1,482,330 control chromosomes in the GnomAD database, including 24,441 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 (4415 hom., cov: 32)
  • Exomes 𝑓: 0.15 (20026 hom.)
• Consequence: LAP3P2 ENST00000454686.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 2 publications found

Genes affected

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

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANDAR	NR_109836.1	n.718A>C		non_coding_transcript_exon_variant	Exon 1 of 1
LAP3P2		n.36674409T>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAP3P2	ENST00000454686.1	n.593T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
PANDAR	ENST00000629595.1	n.718A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33037 AN: 151672 Hom.: 4400 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.420

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: 0.150 AC: 200185 AN: 1330540 Hom.: 20026 Cov.: 23 AF XY: 0.148 AC XY: 99085 AN XY: 668750

African (AFR) AF: 0.321 AC: 9582 AN: 29882

American (AMR) AF: 0.413 AC: 17966 AN: 43526

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 2311 AN: 25246

East Asian (EAS) AF: 0.467 AC: 18121 AN: 38762

South Asian (SAS) AF: 0.109 AC: 9141 AN: 83506

European-Finnish (FIN) AF: 0.111 AC: 5931 AN: 53194

Middle Eastern (MID) AF: 0.170 AC: 920 AN: 5424

European-Non Finnish (NFE) AF: 0.128 AC: 127442 AN: 995230

Other (OTH) AF: 0.157 AC: 8771 AN: 55770

GnomAD4 genome AF: 0.218 AC: 33096 AN: 151790 Hom.: 4415 Cov.: 32 AF XY: 0.219 AC XY: 16232 AN XY: 74194

African (AFR) AF: 0.329 AC: 13611 AN: 41326

American (AMR) AF: 0.322 AC: 4917 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2153 AN: 5138

South Asian (SAS) AF: 0.122 AC: 585 AN: 4796

European-Finnish (FIN) AF: 0.118 AC: 1240 AN: 10540

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.142 AC: 9623 AN: 67944

Other (OTH) AF: 0.218 AC: 459 AN: 2106

Alfa AF: 0.185 Hom.: 434

Bravo AF: 0.246

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.58

Splicing

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

Other links and lift over

dbSNP: rs4714002; hg19: chr6-36642186; COSMIC: COSV55191169;