rs36221778

Positions:

• chr21-45004732-T-C

Variant summary

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

The 21-45004732-T-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,194 control chromosomes in the GnomAD database, including 757 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 0.090 (757 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PICSAR NR_024089.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

Genes affected

PICSAR (HGNC:19725): (P38 inhibited cutaneous squamous cell carcinoma associated lincRNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICSAR	NR_024089.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PICSAR	ENST00000615826.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13664 AN: 152076 Hom.: 756 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0703

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0500 AC: 1 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0898 AC: 13674 AN: 152194 Hom.: 757 Cov.: 32 AF XY: 0.0891 AC XY: 6633 AN XY: 74406

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.0678

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0268

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.0626

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0816 Hom.: 69

Bravo AF: 0.0928

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36221778; hg19: chr21-46424647;