rs1181868

Positions:

• chr1-3734562-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.*1483G>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 152,180 control chromosomes in the GnomAD database, including 26,302 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 (26263 hom., cov: 32)
  • Exomes 𝑓: 0.78 (39 hom.)
• Consequence: TP73 NM_005427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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	UniProt
TP73	NM_005427.4	c.*1483G>T		3_prime_UTR_variant	14/14	ENST00000378295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP73	ENST00000378295.9	c.*1483G>T		3_prime_UTR_variant	14/14	1	NM_005427.4	P1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81938 AN: 151934 Hom.: 26260 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.781 AC: 100 AN: 128 Hom.: 39 Cov.: 0 AF XY: 0.798 AC XY: 67 AN XY: 84

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.539 AC: 81948 AN: 152052 Hom.: 26263 Cov.: 32 AF XY: 0.533 AC XY: 39604 AN XY: 74328

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.587

Alfa AF: 0.694 Hom.: 46606

Bravo AF: 0.519

Asia WGS AF: 0.364 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.54

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: rs1181868; hg19: chr1-3651126;