rs2273953

Positions:

• chr1-3682336-G-A
• chr1-3682336-G-T

Variant summary

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

The NM_005427.4(TP73):​c.-30G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,494,602 control chromosomes in the GnomAD database, including 32,109 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 0.19 (2816 hom., cov: 34)
  • Exomes 𝑓: 0.21 (29293 hom.)
• Consequence: TP73 NM_005427.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP73	NM_005427.4	c.-30G>A		5_prime_UTR_variant	2/14	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.-30G>A		5_prime_UTR_variant	2/14	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28373 AN: 152084 Hom.: 2813 Cov.: 34

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.203 AC: 27759 AN: 136584 Hom.: 2936 AF XY: 0.198 AC XY: 14293 AN XY: 72334

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.227

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.206 AC: 276765 AN: 1342398 Hom.: 29293 Cov.: 31 AF XY: 0.204 AC XY: 134375 AN XY: 658662

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.187 AC: 28394 AN: 152204 Hom.: 2816 Cov.: 34 AF XY: 0.188 AC XY: 13982 AN XY: 74410

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.194

Alfa AF: 0.122 Hom.: 286

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.1
DANN	Benign	0.74

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: rs2273953; hg19: chr1-3598900; COSMIC: COSV60702093; COSMIC: COSV60702093;