rs4711461

Variant names:

• chr6-36674391-C-T
• rs4711461
• ENST00000454686.1:n.575C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANDAR	NR_109836.1	n.736G>A		non_coding_transcript_exon_variant	Exon 1 of 1
LAP3P2		n.36674391C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAP3P2	ENST00000454686.1	n.575C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
PANDAR	ENST00000629595.1	n.736G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32973 AN: 151904 Hom.: 4401 Cov.: 32

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.: 21 AF XY: 0.148 AC XY: 96523 AN XY: 652434

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

GnomAD4 genome AF: 0.217 AC: 33032 AN: 152022 Hom.: 4416 Cov.: 32 AF XY: 0.218 AC XY: 16197 AN XY: 74316

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: 46 AN: 292

European-Non Finnish (NFE) AF: 0.142 AC: 9638 AN: 67968

Other (OTH) AF: 0.219 AC: 462 AN: 2114

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.4
DANN	Benign	0.88
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs4711461; hg19: chr6-36642168; COSMIC: COSV55191162;