rs4711459

Variant names:

• chr6-36674247-T-C
• rs4711459
• ENST00000454686.1:n.431T>C

Variant summary

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

The ENST00000454686.1(LAP3P2):​n.431T>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 0.165 in 1,556,582 control chromosomes in the GnomAD database, including 27,015 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 (4459 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22556 hom.)
• Consequence: LAP3P2 ENST00000454686.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• 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=-0.99).
• 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.880A>G		non_coding_transcript_exon_variant	Exon 1 of 1
LAP3P2		n.36674247T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAP3P2	ENST00000454686.1	n.431T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
PANDAR	ENST00000629595.1	n.880A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33110 AN: 151962 Hom.: 4444 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.159 AC: 223098 AN: 1404502 Hom.: 22556 Cov.: 29 AF XY: 0.156 AC XY: 109396 AN XY: 701666

African (AFR) AF: 0.335 AC: 10782 AN: 32228

American (AMR) AF: 0.419 AC: 18627 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.0958 AC: 2470 AN: 25776

East Asian (EAS) AF: 0.470 AC: 18500 AN: 39378

South Asian (SAS) AF: 0.113 AC: 9631 AN: 85092

European-Finnish (FIN) AF: 0.112 AC: 5977 AN: 53242

Middle Eastern (MID) AF: 0.176 AC: 985 AN: 5586

European-Non Finnish (NFE) AF: 0.138 AC: 146487 AN: 1060338

Other (OTH) AF: 0.165 AC: 9639 AN: 58364

GnomAD4 genome AF: 0.218 AC: 33169 AN: 152080 Hom.: 4459 Cov.: 32 AF XY: 0.219 AC XY: 16269 AN XY: 74374

African (AFR) AF: 0.329 AC: 13640 AN: 41434

American (AMR) AF: 0.322 AC: 4921 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2176 AN: 5172

South Asian (SAS) AF: 0.121 AC: 585 AN: 4820

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10612

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

European-Non Finnish (NFE) AF: 0.142 AC: 9633 AN: 67990

Other (OTH) AF: 0.216 AC: 455 AN: 2106

Alfa AF: 0.187 Hom.: 1560

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	-0.99
CADD	Benign	3.4
DANN	Benign	0.40
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs4711459; hg19: chr6-36642024;