rs12121865

Positions:

• chr1-3690596-G-A
• chr1-3690596-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005427.4(TP73):​c.186+7416G>A variant causes a intron change. The variant allele was found at a frequency of 0.0586 in 1,256,496 control chromosomes in the GnomAD database, including 2,437 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 0.040 (161 hom., cov: 33)
  • Exomes 𝑓: 0.061 (2276 hom.)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.07

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP73	NM_005427.4	c.186+7416G>A		intron_variant		ENST00000378295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP73	ENST00000378295.9	c.186+7416G>A		intron_variant		1	NM_005427.4	P1

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6055 AN: 152228 Hom.: 161 Cov.: 33

Gnomad AFR AF: 0.00991

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0612 AC: 67560 AN: 1104150 Hom.: 2276 AF XY: 0.0602 AC XY: 31752 AN XY: 527706

Gnomad4 AFR exome AF: 0.00850

Gnomad4 AMR exome AF: 0.0328

Gnomad4 ASJ exome AF: 0.0409

Gnomad4 EAS exome AF: 0.0000477

Gnomad4 SAS exome AF: 0.0161

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0677

Gnomad4 OTH exome AF: 0.0565

GnomAD4 genome AF: 0.0397 AC: 6055 AN: 152346 Hom.: 161 Cov.: 33 AF XY: 0.0382 AC XY: 2847 AN XY: 74490

Gnomad4 AFR AF: 0.00988

Gnomad4 AMR AF: 0.0437

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0402

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0149 Hom.: 8

Bravo AF: 0.0397

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.76

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: rs12121865; hg19: chr1-3607160;