rs3765731

Positions:

• chr1-3695328-G-A
• chr1-3695328-G-T

Variant summary

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

The ENST00000378295.9(TP73):​c.186+12148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,136 control chromosomes in the GnomAD database, including 5,125 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 0.25 (5125 hom., cov: 34)
• Consequence: TP73 ENST00000378295.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP73	NM_005427.4	c.186+12148G>A		intron_variant		ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.186+12148G>A		intron_variant		1	NM_005427.4	ENSP00000367545	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38382 AN: 152018 Hom.: 5127 Cov.: 34

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38375 AN: 152136 Hom.: 5125 Cov.: 34 AF XY: 0.249 AC XY: 18552 AN XY: 74364

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.254

Alfa AF: 0.279 Hom.: 9018

Bravo AF: 0.242

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.38

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: rs3765731; hg19: chr1-3611892; COSMIC: COSV60699745; COSMIC: COSV60699745;