rs10910018

Positions:

• chr1-3734845-G-A

Variant summary

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

The NM_005427.4(TP73):​c.*1766G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 151,890 control chromosomes in the GnomAD database, including 238 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 0.036 (238 hom., cov: 33)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: TP73 NM_005427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP73	NM_005427.4	c.*1766G>A		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.*1766G>A		3_prime_UTR_variant	14/14	1	NM_005427.4	ENSP00000367545	P1

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5435 AN: 151606 Hom.: 239 Cov.: 33

Gnomad AFR AF: 0.00817

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0312

GnomAD4 exome AF: 0.0298 AC: 5 AN: 168 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 5 AN XY: 130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0358 AC: 5429 AN: 151722 Hom.: 238 Cov.: 33 AF XY: 0.0369 AC XY: 2740 AN XY: 74200

Gnomad4 AFR AF: 0.00814

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.0389

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0387 Hom.: 43

Bravo AF: 0.0340

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.57

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: rs10910018; hg19: chr1-3651409;