rs1181869

Positions:

• chr1-3734534-C-T

Variant summary

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

The NM_005427.4(TP73):​c.*1455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,078 control chromosomes in the GnomAD database, including 26,253 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 0.54 (26235 hom., cov: 32)
  • Exomes 𝑓: 0.74 (18 hom.)
• Consequence: TP73 NM_005427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

Genes affected

TP73 (HGNC:12003): (tumor protein p73) This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined. [provided by RefSeq, Feb 2011]

TP73 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP73	NM_005427.4	c.*1455C>T		3_prime_UTR_variant	14/14	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.*1455C>T		3_prime_UTR_variant	14/14	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81888 AN: 151892 Hom.: 26233 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.735 AC: 50 AN: 68 Hom.: 18 Cov.: 0 AF XY: 0.722 AC XY: 39 AN XY: 54

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.539 AC: 81897 AN: 152010 Hom.: 26235 Cov.: 32 AF XY: 0.532 AC XY: 39572 AN XY: 74324

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.588

Alfa AF: 0.630 Hom.: 4101

Bravo AF: 0.519

Asia WGS AF: 0.360 AC: 1250 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	0.36
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1181869; hg19: chr1-3651098;