rs4711458

Variant names:

• chr6-36674164-T-C
• rs4711458
• ENST00000454686.1:n.348T>C

Variant summary

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

The ENST00000454686.1(LAP3P2):​n.348T>C 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 0.163 in 1,537,406 control chromosomes in the GnomAD database, including 26,385 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 (4464 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21921 hom.)
• Consequence: LAP3P2 ENST00000454686.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 3 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=-0.63).
• 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.963A>G		non_coding_transcript_exon_variant	Exon 1 of 1
LAP3P2		n.36674164T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAP3P2	ENST00000454686.1	n.348T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
PANDAR	ENST00000629595.1	n.963A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33122 AN: 151978 Hom.: 4449 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.143

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: 0.155

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.157 AC: 217322 AN: 1385310 Hom.: 21921 Cov.: 26 AF XY: 0.154 AC XY: 106925 AN XY: 693632

African (AFR) AF: 0.331 AC: 10488 AN: 31728

American (AMR) AF: 0.419 AC: 18642 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 2451 AN: 25654

East Asian (EAS) AF: 0.469 AC: 18392 AN: 39244

South Asian (SAS) AF: 0.113 AC: 9543 AN: 84684

European-Finnish (FIN) AF: 0.113 AC: 6005 AN: 53352

Middle Eastern (MID) AF: 0.175 AC: 961 AN: 5496

European-Non Finnish (NFE) AF: 0.136 AC: 141425 AN: 1042844

Other (OTH) AF: 0.163 AC: 9415 AN: 57764

GnomAD4 genome AF: 0.218 AC: 33181 AN: 152096 Hom.: 4464 Cov.: 32 AF XY: 0.219 AC XY: 16273 AN XY: 74366

African (AFR) AF: 0.329 AC: 13653 AN: 41470

American (AMR) AF: 0.322 AC: 4923 AN: 15284

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

East Asian (EAS) AF: 0.421 AC: 2178 AN: 5172

South Asian (SAS) AF: 0.122 AC: 586 AN: 4816

European-Finnish (FIN) AF: 0.118 AC: 1249 AN: 10598

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9626 AN: 67970

Other (OTH) AF: 0.217 AC: 458 AN: 2112

Alfa AF: 0.188 Hom.: 462

Bravo AF: 0.246

Asia WGS AF: 0.251 AC: 874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.38
DANN	Benign	0.52
PhyloP100		0.13

Splicing

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

Other links and lift over

dbSNP: rs4711458; hg19: chr6-36641941;