chr1-3700037-C-T

Position:

• chr1-3700037-C-T

Variant summary

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

The NM_005427.4(TP73):​c.187-7512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,644 control chromosomes in the GnomAD database, including 8,802 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 0.33 (8802 hom., cov: 30)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP73	NM_005427.4	c.187-7512C>T		intron_variant		ENST00000378295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP73	ENST00000378295.9	c.187-7512C>T		intron_variant		1	NM_005427.4	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49979 AN: 151528 Hom.: 8789 Cov.: 30

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.330 AC: 50029 AN: 151644 Hom.: 8802 Cov.: 30 AF XY: 0.332 AC XY: 24573 AN XY: 74088

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.317

Alfa AF: 0.357 Hom.: 15679

Bravo AF: 0.315

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.61

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: rs3765736; hg19: chr1-3616601; COSMIC: COSV60699140;