rs4714002

chr6-36674409-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_109836.1(PANDAR):n.718A>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 0.157 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: PANDAR NR_109836.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PANDAR	NR_109836.1	n.718A>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAP3P2	ENST00000454686.1	n.593T>G		non_coding_transcript_exon_variant	1/1
PANDAR	ENST00000629595.1	n.718A>C		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.0915

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.157

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

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.218

Alfa AF: 0.179 Hom.: 395

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

Splicing

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

Publications

LitVar

Other links and lift over

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